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Article

Genomic Characterization of a Carbapenem-Resistant Acinetobacter pittii Strain Harboring Chromosome-Borne blaNDM-1 from China

by
Wenjuan Liu
1,
Haixia Wang
1,
Weijian Zhu
2,
Xiaobin Li
3,4,*,
Ying He
2,* and
Wen Su
5,*
1
Department of Pulmonary and Critical Care Medicine, Yantaishan Hospital, Yantai 264000, China
2
Department of Hematology & Rheumatology, Zhuhai People’s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai 519000, China
3
Department of Pulmonary and Critical Care Medicine, Zhuhai People’s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai 519000, China
4
Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai 519000, China
5
Zhuhai Precision Medical Center, Zhuhai People’s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai 519000, China
*
Authors to whom correspondence should be addressed.
Pathogens 2025, 14(10), 1037; https://doi.org/10.3390/pathogens14101037 (registering DOI)
Submission received: 20 August 2025 / Revised: 23 September 2025 / Accepted: 9 October 2025 / Published: 13 October 2025
(This article belongs to the Special Issue Drug Resistant Pathogens: Diagnosis, Treatment, and Global Health Implications)
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Versions Notes

Abstract

New Delhi metallo-beta-lactamase (NDM)-producing Acinetobacter spp. have been reported worldwide and become a global threat to clinics. This study aimed to characterize the genomic features of the carbapenem-resistant Acinetobacter pittii strain AP8900 harboring chromosome-borne blaNDM-1. The genome of strain AP8900 was fully sequenced using Illumina and PacBio platforms. Genome analyses revealed that the chromosome-borne blaNDM-1 of strain AP8900 was located on the Tn125 bracketed by two copies of ISAba125 in the same orientation. So far, only five strains of A. pittii with complete genomes harboring chromosome-borne blaNDM-1 were found (four from China and one from the USA), all carrying nearly identical Tn125 carried by the strain AP8900. Furthermore, the Tn125 of strain AP8900 in this study was also distributed in other species, mainly Acinetobacter spp. Notably, the Tn125 carried by AP8900 also found in Proteus mirabilis, Klebsiella pneumoniae, and Morganella morganii. In addition, two antibiotic resistance plasmids were found in strain AP8900, and the configuration “sul2- glmM” was found on both pAP8900-1 (ISAba1-sul2-glmM-ISVsa3-IS1006) and pAP8900-2 (∆ISAba2-sul2-glmM-IS17). This study delivers comprehensive insights into the characteristics and diversity of chromosome-borne blaNDM-1 in A. pittii. The complete genome of A. pittii AP8900 strain from southern China provides important data for the analysis of antimicrobial resistance in this region.

1. Introduction

According to the Ambler Classification system, β-lactamases can be divided into four classes (A, B, C, and D) [1]. New Delhi metallo-beta-lactamase (NDM), an Ambler class B beta-lactamase, can hydrolyze nearly all beta-lactam antibiotics, including carbapenems [2]. The first report of NDM-1 was in a Klebsiella pneumoniae isolate recovered in a Swedish patient who had been hospitalized in New Delhi, India, in 2008 [3]. Since then, NDM-1 and its variants have been identified in different species of Enterobacteriaceae, Pseudomonas, and Acinetobacter [4]. According to the records of the beta-lactamase database [5], on 9 January 2025, more than 79 variants of NDM have been identified. The NDM-1 and its variants are continuously spreading globally [4,6], and NDM-producing bacterial pathogens have posed significant therapeutic challenge for clinicians and have attracted considerable attention [7,8].
Acinetobacter spp. are frequently associated with nosocomial infections, such as aspiration pneumonia, catheter-associated bacteremia, soft tissue infection, and urinary tract infection [9,10]. Infections caused by Acinetobacter spp. are among the most difficult to treat because of the multidrug resistance in this genus mediated by the horizontal acquisition of resistance genes or overexpression of the efflux pumps system [11,12]. Although Acinetobacter baumannii receives more attention in genus Acinetobacter, Acinetobacter pittii is an emerging opportunistic nosocomial pathogen [13,14], which is the important member of the Acinetobacter calcoaceticus-baumannii complex [15]. A. pittii has been an emerging concern in nosocomial infection because of its increasing prevalence and multidrug resistance [16].
The blaNDM genes have appeared in various genetic contexts, implying that multiple mechanisms have facilitated the mobilization of blaNDM [17]. The blaNDM has been found to be located on many conjugative and mobilizable plasmids in different species of Enterobacteriaceae and Acinetobacter [4,18,19]. In addition, numerous mobile elements, including ISAba125, IS26, IS3000, IS5, ISCR1, Tn125, Tn3, and Tn3000, are thought to play crucial roles in the dissemination of blaNDM [4,20]. In Acinetobacter spp., the blaNDM has been reported to be embedded in composite transposon Tn125 [21,22,23], bracketed by two copies of the ISAba125 in the same orientation, all carrying the nearly identical Tn125 carried by AP8900, which was initially identified in A. baumannii isolate 161/07, A. baumannii isolate JH, and A. baumannii isolate ML [22]. Current evidence suggests that Tn125 serves as the primary vehicle for blaNDM gene dissemination within Acinetobacter populations, with the ISAba125 elements likely playing a crucial role in its horizontal transfer mechanisms [22]. Currently, studies specific to the characteristics and diversity of chromosome-borne blaNDM in Acinetobacter spp. are scarce. As whole-genome sequencing data grows, there is a demand for extensive analysis of chromosome-borne blaNDM in Acinetobacter spp.
In the present study, we characterized the genomic features of the carbapenem-resistant A. pittii strain AP8900 harboring chromosome-borne blaNDM-1. This study provides deep insights into the characteristics and diversity of chromosome-borne blaNDM in Acinetobacter spp. as well as the acquisition and spread of the blaNDM.

2. Materials and Methods

2.1. Isolation and Characterization of the Strain AP8900

The strain AP8900 was isolated from the sputum sample obtained from a 60-year-old patient at the Zhuhai People’s Hospital in year 2022. The fully automatic VITEK 2 COMPACT system (BioMérieux, Marcy-l’Etoile, France) was used for strain identification as well as the antimicrobial susceptibility testing. The results of antimicrobial susceptibility testing were interpreted according to the Clinical and Laboratory Standards Institute (CLSI M100–S32) (CLSI, 2022). Species identification of the strain AP8900 was also identified by 16S rRNA gene sequencing [24].

2.2. Whole-Genome Sequencing, Assembly, and Annotation

Whole-genome sequencing of the strain AP8900 was conducted using both Illumina NovaSeq 6000 platform and PacBio Sequel IIe platform. The assembly of PacBio reads was performed using Hifiasm (version 0.13-r308)/Canu (version 1.7), and then assembly polishing were conducted using Pilon (version 1.22) [25] with Illumina reads. The completed genome of strain AP8900 were submitted to the NCBI GenBank database [26] and annotated using the NCBI Prokaryotic Annotation Pipeline [27].

2.3. Bioinformatics Analysis Towards the Genome of Strain AP8900

Acquired antibiotic resistance genes (ARGs) carried by the genome of strain AP8900 were detected using software ResFinder version 4.1 [28] at 90% identity and 60% coverage (default parameters of ResFinder). Insertion sequences (ISs) adjacent to ARGs in the genomes of the strain AP8900 were identified by submitting the corresponding gene sequences to ISfinder [29] with default parameters. Nucleotide sequence similarity analysis was performed using MegaBLAST (https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastn&PAGE_TYPE=BlastSearch&LINK_LOC=blas%E2%80%A6, accessed on 19 August 2025) (optimized for aligning DNA queries) [30] against the nucleotide non-redundant (nr) database of GenBank. The sequence comparison was performed and visualized using Easyfig version 2.2.5 [31] and BRIG version 0.95 [32].

2.4. Identification of the Bacteria Harboring Chromosome-Borne blaNDM Available in GenBank Database

We performed MegaBLAST analysis of the blaNDM-1 gene sequence against the GenBank non-redundant (nr) database to identify sequences harboring blaNDM, applying thresholds of 100.00% coverage and >99.00% identity. Then, we selected the bacterial strains harboring chromosome-borne blaNDM with complete genome. The variants of blaNDM were further determined by software ResFinder 4.1 [28], and the genetic contexts of the chromosome-borne blaNDM genes were analyzed using software ISfinder [29].

3. Results

3.1. Antibiotic Resistance Profiles of the Carbapenem-Resistant and Multidrug-Resistant A. pittii Strain AP8900

Antimicrobial susceptibility testing results indicated that the A. pittii strain AP8900 in our study exhibited resistance to the cephalosporins (cefepime and ceftazidime), carbapenem (imipenem), quinolones (ciprofloxacin and levofloxacin), sulfamethoxazole/trimethoprim, and β-lactam/β-lactamase inhibitor combinations (ticarcillin/clavulanate and piperacillin/tazobactam) (Table 1). Additionally, it also exhibited an intermediate resistance to meropenem (Table 1).

3.2. Genomic Characteristics of the Carbapenem-Resistant A. pittii Strain AP8900

The fully sequenced genome of the A. pittii strain AP8900 compised a circular chromosome with 3,966,182 bp (GenBank accession CP123765) and four plasmids, including one 86,394 bp plasmid (pAP8900-1, GenBank accession CP123766), one 43,600 bp plasmid (pAP8900-2, GenBank accession CP123767), one 12,558 bp plasmid (pAP8900-3, GenBank accession CP123768), and one 11,346 bp plasmid (pAP8900-4, GenBank accession CP123769).
The results of ResFinder showed that the acquired ARGs were distributed on both chromosome and the plasmids (pAP8900-1 and pAP8900-2). The chromosome of A. pittii strain AP8900 carried three beta-lactam resistance genes (blaADC-25, blaNDM-1, and blaOXA-526). The plasmid pAP8900-1 carried one sulphonamide resistance gene (sul2). The plasmid pAP8900-2 harbored the acquired ARGs including genes encoding resistance to macrolide (msr(E) and mph(E)), tetracycline (tet(39)- tetR), chloramphenicol (cml), sulphonamide (sul2), and aminoglycoside (aph(3″)-Ib and aph(6)-Id).
Genetic context of chromosome-borne blaNDM-1 in the carbapenem-resistant A. pittii strain AP8900
The chromosome-borne blaNDM-1 of AP8900 was located on the approximately 10-kb composite transposon Tn125, bracketed by two copies of insertion sequence ISAba125 in the same orientation. The blaNDM-1 was flanked by ISAba125 and a bleomycin resistance gene, bleMBL, located adjacent to trpF-dsbC-cutA-groES-groEL. The ISCR27 was found to be located downstream of the groEL. The Tn125 of A. pittii AP8900 was nearly identical to those of A. baumannii 161/07 (100.00% coverage and 99.96% identity), A. baumannii isolate JH (100.00% coverage and 99.87% identity), and A. baumannii isolate ML (100.00% coverage and 99.86% identity), which were initially identified Tn125 (Figure 1).

3.3. Bacteria Harboring Chromosome-Borne blaNDM Available in GenBank Database

BLASTn analysis using the DNA sequence of the blaNDM-1 gene of AP8900 against the GenBank nr database (24 December 2024) revealed 2774 total hits, of which 204 were complete genome sequences harboring the chromosome-borne blaNDM, with blaNDM-1 being the most dominant (176 strains harboring blaNDM-1), followed by the blaNDM-5 (20 strains harboring blaNDM-5) (Figure 2A). The hosts harboring chromosome-borne blaNDM were widespread, involving 15 different genera, with Acinetobacter (66 strains), Pseudomonas (43 strains), Klebsiella (18 strains), Proteus (18 strains), and Escherichia (15 strains) being the TOP5 genera (Figure 2B). At the species level, the most common species harboring chromosome-borne blaNDM was A. baumannii (48 strains), followed by Pseudomonas aeruginosa (38 strains), K. pneumoniae (18 strains), Proteus mirabilis (18 strains), and Escherichia coli (15 strains) (Figure 2C). So far, only five strains of A. pittii with complete genomes harboring chromosome-borne blaNDM (all blaNDM-1) were found, including four strains from China (Hefei, Hangzhou, Luzhou, and Zhuhai) and one strain from the USA (Figure 3). Notably, four of these five strains harbored the nearly identical Tn125 carried by AP8900 in our study (100.00% coverage and >99.00% identity) (Figure 3). The A. pittii strain AP8900 was the first reported with a complete genome in southern China.
The distribution of Tn125 carried by AP8900 in this study was also explored in other strains with complete genomes harboring chromosome-borne blaNDM. Based on the DNA sequence of Tn125 carried by AP8900, the BLAST searches against the 204 bacterial strains with complete genome harboring chromosome-borne blaNDM indicated that the Tn125 carried by AP8900 was present on 57 bacterial strains (100.00% coverage and >99.00% identity). Notably, 49 of the 57 bacterial strains harboring the 10-kb Tn125 carried by AP8900 were found to belong to the Acinetobacter genus, including 11 species, accounting for 85.96% of all the 57 bacterial strains carrying Tn125 carried by AP8900. In addition, Tn125 carried by AP8900 was also found in P. mirabilis (four strains), K. pneumoniae (three strains), and Morganella morganii (one strain) (Table 2).

3.4. Genomic Analysis of the Antibiotic-Resistant Plasmids Carried by A. pittii Strain AP8900

For the plasmid pAP8900-1 of A. pittii strain AP8900, the sulphonamide resistance gene (sul2) and one phosphoglucosamine mutase gene (glmM) were bracketed by ISAba1 and ISVsa3-IS1006. For the pAP8900-2, one insertion sequence ISAba43 was located upstream of the chloramphenicol resistance gene cml, adjacent to the macrolide resistance genes msr(E)-mph(E) and the tetracycline resistance genes tet(39)-tetR. Notably, the “sul2-glmM” present in the pAP8900-1 was also found on the pAP8900-2, which was bracketed by ∆ISAba2 and IS17, adjacent to the aminoglycoside resistance genes aph(3″)-Ib-aph(6)-Id (Figure 4).
Based on the results of the BLAST search against the GenBank nr database, the 86.39-kb plasmid pAP8900-1 had high similarity with the plasmid pSP19M058-1 in A. pittii strain 19MO01SH04 (99.00% coverage and 99.99% identity), the plasmid in A. pittii strain ST220 (100.00% coverage and 99.82% identity), and the plasmid pTCM-1 in A. pittii strain TCM (100.00% coverage and 99.93% identity) (Figure 4A). In addition, BLAST search against the GenBank nr database also showed that the 43.60-kb plasmid pAP8900-2 was highly similar to the plasmid pAP2044-2 in A. pittii strain AP2044 (100.00% coverage and 99.92% identity), the plasmid pSP19M058-4 in A. pittii strain 19MO01SH04 (100.00% coverage and 99.99% identity), and the plasmid pA1269-1 in A. pittii strain A1269 (100.00% coverage and 100.00% identity) (Figure 4B).

4. Discussion

In this study, the carbapenem-resistant A. pittii strain AP8900 harbored the chromosome-borne carbapenemase gene blaNDM-1. The NDM-type carbapenemases are quickly spreading and the troublesome family of Ambler class B β-lactamases, and NDM-producing Acinetobacter spp., has been recently reported in numerous countries, particularly the predominant NDM-1 type [7,8]. The first global report of NDM-producing clinical Acinetobacter strain was made in 2010 when blaNDM-1-positive A. baumannii was found in India [33]. The first report of blaNDM-1-positive clinical isolates in China occurred in 2010, with four A. baumannii isolates identified in different provinces [34]. Since then, blaNDM-1 has been detected numerous times in different strains of Acinetobacter, such as Acinetobacter junii, Acinetobacter lwoffii, and A. pittii, which were isolated from the clinical, environmental, and farm animal samples in China [34,35,36,37]. In this study, we found that the bacterial hosts harboring chromosome-borne blaNDM were widespread, involving 15 different genera, with Acinetobacter and Pseudomonas being the most common. Infections caused by carbapenem-resistant Gram-negative bacteria (GNB) pose a significant threat due to their high morbidity and mortality rates [38,39]. Infections caused by NDM-producing bacteria are generally more challenging to treat than those caused by KPC-producing bacteria. For example, ceftazidime–avibactam (CAZ-AVI), a novel last-resort β-lactam antibiotic, is effective against KPC-producing bacterial infections but lacks activity against NDM-producing strains [40]. Notably, new antibiotics classes such as Trojan Horse antibiotics [41] and antibiotics targeting bacterial metallophores [42] represent promising therapeutic options for infections caused by NDM-producing strains.
In this study, the blaNDM-1 of strain AP8900 was found to locate on the composite transposon Tn125, which is bracketed by two ISAba125s in the same orientation, forming the structure “ISAba125-blaNDM-1-bleMBL-trpF-dsbC-cutA-groES-groEL-ISCR27-ISAba125.” Notably, only five strains of A. pittii with complete genomes harboring chromosome-borne blaNDM (all blaNDM-1) were found, all carrying the nearly identical Tn125 carried by AP8900, which was highly similar to the initially identified Tn125 [22]. The 1087 bp insertion sequence ISAba125 carried by Tn125 belongs to a member of the IS30 family of insertion elements [22,43]. It has been suggested that the blaNDM gene has been acquired into Acinetobacter spp. from the environment and then has spread to the Enterobacteriaceae with the help of the ISAba125 [44]. Notably, for the Tn125, the ISAba125 upstream of the blaNDM has been reported to provide the -35 region of a promoter necessary for the expression of blaNDM-1 [45]. In addition to blaNDM-1, the ISAba125 was also reported to activate the horizontal transfer of ampC gene among A. baumannii strains leading to cephalosporin resistance [46]. The groES-groEL-ISCR27 section (adjacent to the other copy of ISAba125) may originate from Xanthomonas sp. [47]. It is hypothesized that ISCR27, employing a rolling-circle transposition mechanism [48], initially mediated the ancestral mobilization of blaNDM in Xanthomonas sp. and precisely positioned it downstream of ISAba125 [22,47]. Moreover, the consistent presence of ISAba125 in all blaNDM-positive strains so far, along with early observations in A. baumannii, proposed that Tn125 was the ancestral transposon facilitating the mobilization of blaNDM, and A. baumannii was its ancestral host [47,49].
In this study, two antibiotic resistance plasmids were found in A. pittii strain AP8900. Notably, the configuration “sul2-glmM” was found to locate both on the pAP8900-1 (ISAba1-sul2-glmM-ISVsa3-IS1006) and the pAP8900-2 (∆ISAba2-sul2-glmM-IS17) of the A. pittii strain AP8900. The “sul2-glmM” was also reported in other configurations of Acinetobacter species. For example, the configuration “ISAba1-sul2-glmM-∆ISCR2”, which was part of Tn6450, was found in Acinetobacter towneri strain SWBY1 [50]; the configuration “ISAba1-sul2-∆glmM-ISCR2-strB-strA” was detected in A. baumannii RUH 875 [51]; and the configuration “ISAba1-sul2-glmM-ISVsa3-lysR-floR-DUF3363-strB-strA-ISAba1” was identified in Acinetobacter johnsonii Acsw19 [52].

5. Conclusions

In summary, we report the complete genome of A. pittii strain AP8900 harboring chromosome-borne blaNDM-1, which was isolated from the sputum of a 60-year-old patient. In strain AP8900, the chromosome-borne blaNDM-1 was located on the Tn125 composite transposon, which was bracketed by two copies of ISAba125 in the same orientation. In addition, two antibiotic resistance plasmids were identified in A. pittii strain AP8900. The complete genome of A. pittii AP8900 strain from southern China provides important data for the analysis of antimicrobial resistance in this region.

Author Contributions

Conceptualization, W.S., Y.H. and X.L.; methodology, W.L.; software, W.L.; validation, W.L. and H.W.; formal analysis, W.Z.; writing—original draft preparation, W.L. and H.W.; writing—review and editing, W.S., Y.H. and X.L.; visualization, W.L.; supervision, W.S. and X.L.; funding acquisition, X.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the grants from the Xiangshan Talent Project of Zhuhai People’s Hospital (Grant No. 2020XSYC-02).

Institutional Review Board Statement

This study has been approved by the Ethics Committee of Zhuhai People’s Hospital (Permission Number: [2023] No. 37 on 24 May 2023).

Informed Consent Statement

The present study was a study focusing on bacteria and did not contain any sensitive personal information. Therefore, informed consent was not required.

Data Availability Statement

The complete genome sequences of the strain AP8900 in this study have been submitted to the GenBank nucleotide database with accession numbers CP123765-CP123769.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
NDMNew Delhi metallo-beta-lactamase
ARGsDirectory of open access journals antibiotic resistance genes

References

  1. Hall, B.G.; Barlow, M. Revised Ambler classification of β-lactamases. J. Antimicrob. Chemother. 2005, 55, 1050–1051. [Google Scholar] [CrossRef]
  2. Wang, T.; Xu, K.; Zhao, L.; Tong, R.; Xiong, L.; Shi, J. Recent research and development of NDM-1 inhibitors. Eur. J. Med. Chem. 2021, 223, 113667. [Google Scholar] [CrossRef]
  3. Yong, D.; Toleman, M.A.; Giske, C.G.; Cho, H.S.; Sundman, K.; Lee, K.; Walsh, T.R. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob. Agents Chemother. 2009, 53, 5046–5054. [Google Scholar] [CrossRef]
  4. Wu, W.; Feng, Y.; Tang, G.; Qiao, F.; McNally, A.; Zong, Z. NDM Metallo-β-Lactamases and Their Bacterial Producers in Health Care Settings. Clin. Microbiol. Rev. 2019, 32, e00115–e00118. [Google Scholar] [CrossRef] [PubMed]
  5. Naas, T.; Oueslati, S.; Bonnin, R.A.; Dabos, M.L.; Zavala, A.; Dortet, L.; Retailleau, P.; Iorga, B.I. Beta-lactamase database (BLDB)–structure and function. J. Enzym. Inhib. Med. Chem. 2017, 32, 917–919. [Google Scholar] [CrossRef]
  6. Albiger, B.; Glasner, C.; Struelens, M.J.; Grundmann, H.; Monnet, D.L. Carbapenemase-producing Enterobacteriaceae in Europe: Assessment by national experts from 38 countries, May 2015. Eurosurveillance 2015, 20, 17–34. [Google Scholar] [CrossRef]
  7. Walsh, T.R.; Weeks, J.; Livermore, D.M.; Toleman, M.A. Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: An environmental point prevalence study. Lancet Infect. Dis. 2011, 11, 355–362. [Google Scholar] [CrossRef]
  8. Nordmann, P.; Poirel, L.; Walsh, T.R.; Livermore, D.M. The emerging NDM carbapenemases. Trends Microbiol. 2011, 19, 588–595. [Google Scholar] [CrossRef]
  9. Wong, D.; Nielsen, T.B.; Bonomo, R.A.; Pantapalangkoor, P.; Luna, B.; Spellberg, B. Clinical and Pathophysiological Overview of Acinetobacter Infections: A Century of Challenges. Clin. Microbiol. Rev. 2017, 30, 409–447. [Google Scholar] [CrossRef] [PubMed]
  10. Carvalheira, A.; Silva, J.; Teixeira, P. Acinetobacter spp. in food and drinking water—A review. Food Microbiol. 2021, 95, 103675. [Google Scholar] [CrossRef] [PubMed]
  11. Richards, G.A.; Perovic, O.; Brink, A.J. The challenges of difficult-to-treat Acinetobacter infections. Clin. Microbiol. Rev. 2024, 37, e0009324. [Google Scholar] [CrossRef]
  12. Kornelsen, V.; Kumar, A. Update on Multidrug Resistance Efflux Pumps in Acinetobacter spp. Antimicrob. Agents Chemother. 2021, 65, e0051421. [Google Scholar] [CrossRef] [PubMed]
  13. Tierney, B.T.; Singh, N.K.; Simpson, A.C.; Hujer, A.M.; Bonomo, R.A.; Mason, C.E.; Venkateswaran, K. Multidrug-resistant Acinetobacter pittii is adapting to and exhibiting potential succession aboard the International Space Station. Microbiome 2022, 10, 210. [Google Scholar] [CrossRef]
  14. Bello-López, E.; Escobedo-Muñoz, A.S.; Guerrero, G.; Cruz-Córdova, A.; Garza-González, E.; Hernández-Castro, R.; Zarain, P.L.; Morfín-Otero, R.; Volkow, P.; Xicohtencatl-Cortes, J.; et al. Acinetobacter pittii: The emergence of a hospital-acquired pathogen analyzed from the genomic perspective. Front. Microbiol. 2024, 15, 1412775. [Google Scholar] [CrossRef]
  15. Djahanschiri, B.; Di Venanzio, G.; Distel, J.S.; Breisch, J.; Dieckmann, M.A.; Goesmann, A.; Averhoff, B.; Göttig, S.; Wilharm, G.; Feldman, M.F.; et al. Evolutionarily stable gene clusters shed light on the common grounds of pathogenicity in the Acinetobacter calcoaceticus-baumannii complex. PLoS Genet. 2022, 18, e1010020. [Google Scholar] [CrossRef]
  16. Wang, S.; Zhou, Y.; Wang, Y.; Tang, K.; Wang, D.; Hong, J.; Wang, P.; Ye, S.; Yan, J.; Li, S.; et al. Genetic landscape and evolution of Acinetobacter pittii, an underestimated emerging nosocomial pathogen. Commun. Biol. 2025, 8, 738. [Google Scholar] [CrossRef]
  17. Kumari, S.; Narendrakumar, L.; Chawla, M.; Das, S.; Koley, H.; Das, B. Investigating the molecular transmission dynamics of bla(NDM) in antibiotic-selective environments. J. Bacteriol. 2025, 207, e0013325. [Google Scholar] [CrossRef]
  18. Zhang, Z.; Guo, H.; Li, X.; Li, W.; Yang, G.; Ni, W.; Zhan, M.; Lu, L.; Zhang, Z.; Li, X.; et al. Genetic Diversity and Characteristics of bla (NDM)-Positive Plasmids in Escherichia coli. Front. Microbiol. 2021, 12, 729952. [Google Scholar] [CrossRef]
  19. Yehya, A.; Ezzeddine, Z.; Chakkour, M.; Dhaini, Z.; Bou Saba, M.S.; Bou Saba, A.S.; Nohra, L.; Nassar, N.B.; Yassine, M.; Bahmad, H.F.; et al. The intricacies of Acinetobacter baumannii: A multifaceted comprehensive review of a multidrug-resistant pathogen and its clinical significance and implications. Front. Microbiol. 2025, 16, 1565965. [Google Scholar] [CrossRef] [PubMed]
  20. Acman, M.; Wang, R.; van Dorp, L.; Shaw, L.P.; Wang, Q.; Luhmann, N.; Yin, Y.; Sun, S.; Chen, H.; Wang, H.; et al. Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene bla(NDM). Nat. Commun. 2022, 13, 1131. [Google Scholar] [CrossRef] [PubMed]
  21. Pfeifer, Y.; Wilharm, G.; Zander, E.; Wichelhaus, T.A.; Göttig, S.; Hunfeld, K.P.; Seifert, H.; Witte, W.; Higgins, P.G. Molecular characterization of blaNDM-1 in an Acinetobacter baumannii strain isolated in Germany in 2007. J. Antimicrob. Chemother. 2011, 66, 1998–2001. [Google Scholar] [CrossRef] [PubMed]
  22. Poirel, L.; Bonnin, R.A.; Boulanger, A.; Schrenzel, J.; Kaase, M.; Nordmann, P. Tn125-related acquisition of blaNDM-like genes in Acinetobacter baumannii. Antimicrob. Agents Chemother. 2012, 56, 1087–1089. [Google Scholar] [CrossRef]
  23. Bontron, S.; Nordmann, P.; Poirel, L. Transposition of Tn125 Encoding the NDM-1 Carbapenemase in Acinetobacter baumannii. Antimicrob. Agents Chemother. 2016, 60, 7245–7251. [Google Scholar] [CrossRef]
  24. Janda, J.M.; Abbott, S.L. 16S rRNA gene sequencing for bacterial identification in the diagnostic laboratory: Pluses, perils, and pitfalls. J. Clin. Microbiol. 2007, 45, 2761–2764. [Google Scholar] [CrossRef]
  25. Walker, B.J.; Abeel, T.; Shea, T.; Priest, M.; Abouelliel, A.; Sakthikumar, S.; Cuomo, C.A.; Zeng, Q.; Wortman, J.; Young, S.K.; et al. Pilon: An integrated tool for comprehensive microbial variant detection and genome assembly improvement. PLoS ONE 2014, 9, e112963. [Google Scholar] [CrossRef] [PubMed]
  26. Sayers, E.W.; Cavanaugh, M.; Clark, K.; Ostell, J.; Pruitt, K.D.; Karsch-Mizrachi, I. GenBank. Nucleic Acids Res. 2020, 48, D84–D86. [Google Scholar] [CrossRef]
  27. Tatusova, T.; DiCuccio, M.; Badretdin, A.; Chetvernin, V.; Nawrocki, E.P.; Zaslavsky, L.; Lomsadze, A.; Pruitt, K.D.; Borodovsky, M.; Ostell, J. NCBI prokaryotic genome annotation pipeline. Nucleic Acids Res. 2016, 44, 6614–6624. [Google Scholar] [CrossRef]
  28. Bortolaia, V.; Kaas, R.S.; Ruppe, E.; Roberts, M.C.; Schwarz, S.; Cattoir, V.; Philippon, A.; Allesoe, R.L.; Rebelo, A.R.; Florensa, A.F.; et al. ResFinder 4.0 for predictions of phenotypes from genotypes. J. Antimicrob. Chemother. 2020, 75, 3491–3500. [Google Scholar] [CrossRef]
  29. Siguier, P.; Perochon, J.; Lestrade, L.; Mahillon, J.; Chandler, M. ISfinder: The reference centre for bacterial insertion sequences. Nucleic Acids Res. 2006, 34, D32–D36. [Google Scholar] [CrossRef] [PubMed]
  30. Morgulis, A.; Coulouris, G.; Raytselis, Y.; Madden, T.L.; Agarwala, R.; Schäffer, A.A. Database indexing for production MegaBLAST searches. Bioinformatics 2008, 24, 1757–1764. [Google Scholar] [CrossRef]
  31. Sullivan, M.J.; Petty, N.K.; Beatson, S.A. Easyfig: A genome comparison visualizer. Bioinformatics 2011, 27, 1009–1010. [Google Scholar] [CrossRef]
  32. Alikhan, N.F.; Petty, N.K.; Ben Zakour, N.L.; Beatson, S.A. BLAST Ring Image Generator (BRIG): Simple prokaryote genome comparisons. BMC Genom. 2011, 12, 402. [Google Scholar] [CrossRef]
  33. Karthikeyan, K.; Thirunarayan, M.A.; Krishnan, P. Coexistence of blaOXA-23 with blaNDM-1 and armA in clinical isolates of Acinetobacter baumannii from India. J. Antimicrob. Chemother. 2010, 65, 2253–2254. [Google Scholar] [CrossRef]
  34. Chen, Y.; Zhou, Z.; Jiang, Y.; Yu, Y. Emergence of NDM-1-producing Acinetobacter baumannii in China. J. Antimicrob. Chemother. 2011, 66, 1255–1259. [Google Scholar] [CrossRef] [PubMed]
  35. Hu, H.; Hu, Y.; Pan, Y.; Liang, H.; Wang, H.; Wang, X.; Hao, Q.; Yang, X.; Yang, X.; Xiao, X.; et al. Novel plasmid and its variant harboring both a bla(NDM-1) gene and type IV secretion system in clinical isolates of Acinetobacter lwoffii. Antimicrob. Agents Chemother. 2012, 56, 1698–1702. [Google Scholar] [CrossRef]
  36. Yang, J.; Chen, Y.; Jia, X.; Luo, Y.; Song, Q.; Zhao, W.; Wang, Y.; Liu, H.; Zheng, D.; Xia, Y.; et al. Dissemination and characterization of NDM-1-producing Acinetobacter pittii in an intensive care unit in China. Clin. Microbiol. Infect. 2012, 18, E506–E513. [Google Scholar] [CrossRef]
  37. Zhang, C.; Qiu, S.; Wang, Y.; Qi, L.; Hao, R.; Liu, X.; Shi, Y.; Hu, X.; An, D.; Li, Z.; et al. Higher isolation of NDM-1 producing Acinetobacter baumannii from the sewage of the hospitals in Beijing. PLoS ONE 2014, 8, e64857. [Google Scholar] [CrossRef]
  38. Jean, S.S.; Harnod, D.; Hsueh, P.R. Global Threat of Carbapenem-Resistant Gram-Negative Bacteria. Front. Cell. Infect. Microbiol. 2022, 12, 823684. [Google Scholar] [CrossRef] [PubMed]
  39. Paudel, R.; Shrestha, E.; Chapagain, B.; Tiwari, B.R. Carbapenemase producing Gram negative bacteria: Review of resistance and detection methods. Diagn. Microbiol. Infect. Dis. 2024, 110, 116370. [Google Scholar] [CrossRef] [PubMed]
  40. Khoshdel, N.; Noursalehigarakani, M.; Seghatoleslami, Z.S.; Hadavand, F.; Eghbal, E.; Nasiri, M.J.; Simula, E.; Ahmed, P.; Sechi, L.A. Efficacy of Ceftazidime-avibactam in treating Gram-negative infections: A systematic review and meta-analysis. Eur. J. Clin. Microbiol. Infect. Dis. 2025, 44, 767–778. [Google Scholar] [CrossRef]
  41. Tillotson, G.S. Trojan Horse Antibiotics-A Novel Way to Circumvent Gram-Negative Bacterial Resistance? Infect. Dis. 2016, 9, 45–52. [Google Scholar] [CrossRef]
  42. Ezzeddine, Z.; Ghssein, G. Towards new antibiotics classes targeting bacterial metallophores. Microb. Pathog. 2023, 182, 106221. [Google Scholar] [CrossRef]
  43. Mussi, M.A.; Limansky, A.S.; Viale, A.M. Acquisition of resistance to carbapenems in multidrug-resistant clinical strains of Acinetobacter baumannii: Natural insertional inactivation of a gene encoding a member of a novel family of beta-barrel outer membrane proteins. Antimicrob. Agents Chemother. 2005, 49, 1432–1440. [Google Scholar] [CrossRef]
  44. Krishnaraju, M.; Kamatchi, C.; Jha, A.K.; Devasena, N.; Vennila, R.; Sumathi, G.; Vaidyanathan, R. Complete sequencing of an IncX3 plasmid carrying blaNDM-5 allele reveals an early stage in the dissemination of the blaNDM gene. Indian J. Med. Microbiol. 2015, 33, 30–38. [Google Scholar] [CrossRef]
  45. Poirel, L.; Bonnin, R.A.; Nordmann, P. Analysis of the resistome of a multidrug-resistant NDM-1-producing Escherichia coli strain by high-throughput genome sequencing. Antimicrob. Agents Chemother. 2011, 55, 4224–4229. [Google Scholar] [CrossRef]
  46. Hamidian, M.; Hancock, D.P.; Hall, R.M. Horizontal transfer of an ISAba125-activated ampC gene between Acinetobacter baumannii strains leading to cephalosporin resistance. J. Antimicrob. Chemother. 2013, 68, 244–245. [Google Scholar] [CrossRef]
  47. Partridge, S.R.; Iredell, J.R. Genetic contexts of blaNDM-1. Antimicrob. Agents Chemother. 2012, 56, 6065–6067. [Google Scholar] [CrossRef] [PubMed]
  48. Toleman, M.A.; Bennett, P.M.; Walsh, T.R. ISCR elements: Novel gene-capturing systems of the 21st century? Microbiol. Mol. Biol. Rev. 2006, 70, 296–316. [Google Scholar] [CrossRef] [PubMed]
  49. Toleman, M.A.; Spencer, J.; Jones, L.; Walsh, T.R. blaNDM-1 is a chimera likely constructed in Acinetobacter baumannii. Antimicrob. Agents Chemother. 2012, 56, 2773–2776. [Google Scholar] [CrossRef] [PubMed]
  50. Jiang, N.; Zhang, X.; Zhou, Y.; Zhang, Z.; Zheng, X. Whole-genome sequencing of an NDM-1- and OXA-58-producing Acinetobacter towneri isolate from hospital sewage in Sichuan Province, China. J. Glob. Antimicrob. Resist. 2019, 16, 4–5. [Google Scholar] [CrossRef]
  51. Hamidian, M.; Ambrose, S.J.; Hall, R.M. A large conjugative Acinetobacter baumannii plasmid carrying the sul2 sulphonamide and strAB streptomycin resistance genes. Plasmid 2016, 87–88, 43–50. [Google Scholar] [CrossRef] [PubMed]
  52. Tang, L.; Shen, W.; Zhang, Z.; Zhang, J.; Wang, G.; Xiang, L.; She, J.; Hu, X.; Zou, G.; Zhu, B.; et al. Whole-Genome Analysis of Two Copies of bla (NDM-1) Gene Carrying Acinetobacter johnsonii Strain Acsw19 Isolated from Sichuan, China. Infect. Drug Resist. 2020, 13, 855–865. [Google Scholar] [CrossRef] [PubMed]
Pathogens 14 01037 g001
Figure 1. Comparison of the composite transposon Tn125 (harboring the chromosome-borne blaNDM-1) carried by AP8900 with those of A. baumannii isolate ML, A. baumannii isolate JH, and A. baumannii 161/07, which were the initially identified Tn125. Resistance genes, ISs, and other genes are shown in red, blue, and gray, respectively.
Figure 1. Comparison of the composite transposon Tn125 (harboring the chromosome-borne blaNDM-1) carried by AP8900 with those of A. baumannii isolate ML, A. baumannii isolate JH, and A. baumannii 161/07, which were the initially identified Tn125. Resistance genes, ISs, and other genes are shown in red, blue, and gray, respectively.
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Pathogens 14 01037 g002
Figure 2. Statistics of bacterial hosts harboring chromosome-borne blaNDM. (A) Histogram of a number of variants of blaNDM genes among the 204 bacterial strains with complete genomes harboring the chromosome-borne blaNDM. (B) Histogram about the number of the chromosome-borne blaNDM distributed in different genera. (C) Histogram about the number of the chromosome-borne blaNDM distributed in different species.
Figure 2. Statistics of bacterial hosts harboring chromosome-borne blaNDM. (A) Histogram of a number of variants of blaNDM genes among the 204 bacterial strains with complete genomes harboring the chromosome-borne blaNDM. (B) Histogram about the number of the chromosome-borne blaNDM distributed in different genera. (C) Histogram about the number of the chromosome-borne blaNDM distributed in different species.
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Pathogens 14 01037 g003
Figure 3. Comparison of the composite transposon Tn125 carried by the five strains of A. pittii with complete genomes harboring chromosome-borne blaNDM-1. Resistance genes, ISs, and other genes are shown in red, blue, and gray, respectively.
Figure 3. Comparison of the composite transposon Tn125 carried by the five strains of A. pittii with complete genomes harboring chromosome-borne blaNDM-1. Resistance genes, ISs, and other genes are shown in red, blue, and gray, respectively.
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Pathogens 14 01037 g004
Figure 4. Genetic structures of the two antibiotic resistance plasmids were found in A. pittii strain AP8900. (A) Comparison of plasmid pAP8900-1 and the plasmids was highly similar to pAP8900-1. (B) Comparison of plasmid pAP8900-2 and the plasmids was highly similar to pAP8900-2. Resistance and transposase are shown in red and blue, respectively.
Figure 4. Genetic structures of the two antibiotic resistance plasmids were found in A. pittii strain AP8900. (A) Comparison of plasmid pAP8900-1 and the plasmids was highly similar to pAP8900-1. (B) Comparison of plasmid pAP8900-2 and the plasmids was highly similar to pAP8900-2. Resistance and transposase are shown in red and blue, respectively.
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Table 1. Minimum inhibitory concentration (MIC) values of the A. pittii strain AP8900.
Table 1. Minimum inhibitory concentration (MIC) values of the A. pittii strain AP8900.
AntibioticsMIC (μg/mL)Interpretation
CategoriesName
CephalosporinsCeftazidime≥64R
Cefepime≥32R
CarbapenemsImipenem 8R
Meropenem4I
FluoroquinolonesCiprofloxacin≥4R
Levofloxacin≥8R
SulfonamidesSulfamethoxazole/trimethoprim160R
β-lactam/β-lactamase inhibitor combinationsPiperacillin/tazobactam ≥128R
Ticarcillin/clavulanate≤8R
Note: R, Resistant; I, Intermediate.
Table 2. The Tn125 carried by strain AP8900 distributed in the bacterial strains with complete genome harboring chromosome-borne blaNDM.
Table 2. The Tn125 carried by strain AP8900 distributed in the bacterial strains with complete genome harboring chromosome-borne blaNDM.
SpeciesNumber of Strains Harboring Tn125Number of Strains Harboring Chromosome-Borne blaNDMProportion * (%)
Acinetobacter baumannii314864.58
Acinetobacter bereziniae22100.00
Acinetobacter defluvii11100.00
Acinetobacter haemolyticus11100.00
Acinetobacter indicus33100.00
Acinetobacter johnsonii11100.00
Acinetobacter junii11100.00
Acinetobacter pittii55100.00
Acinetobacter sp.11100.00
Acinetobacter variabilis11100.00
Acinetobacter wuhouensis22100.00
Klebsiella pneumoniae31816.67
Morganella morganii1812.50
Proteus mirabilis41822.22
Note: * Proportion represents the percentage of strains harboring Tn125 carried by AP8900 among those carrying chromosome-borne blaNDM.
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Liu, W.; Wang, H.; Zhu, W.; Li, X.; He, Y.; Su, W. Genomic Characterization of a Carbapenem-Resistant Acinetobacter pittii Strain Harboring Chromosome-Borne blaNDM-1 from China. Pathogens 2025, 14, 1037. https://doi.org/10.3390/pathogens14101037

AMA Style

Liu W, Wang H, Zhu W, Li X, He Y, Su W. Genomic Characterization of a Carbapenem-Resistant Acinetobacter pittii Strain Harboring Chromosome-Borne blaNDM-1 from China. Pathogens. 2025; 14(10):1037. https://doi.org/10.3390/pathogens14101037

Chicago/Turabian Style

Liu, Wenjuan, Haixia Wang, Weijian Zhu, Xiaobin Li, Ying He, and Wen Su. 2025. "Genomic Characterization of a Carbapenem-Resistant Acinetobacter pittii Strain Harboring Chromosome-Borne blaNDM-1 from China" Pathogens 14, no. 10: 1037. https://doi.org/10.3390/pathogens14101037

APA Style

Liu, W., Wang, H., Zhu, W., Li, X., He, Y., & Su, W. (2025). Genomic Characterization of a Carbapenem-Resistant Acinetobacter pittii Strain Harboring Chromosome-Borne blaNDM-1 from China. Pathogens, 14(10), 1037. https://doi.org/10.3390/pathogens14101037

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