Antibiotic Resistance and Virulence Mechanisms in Gram-Negative Bacteria: An Alliance for Success

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 3987

Special Issue Editor


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Guest Editor
Department of Science, Roma Tre University, Rome, Italy
Interests: Pseudomonas aeruginosa; Acinetobacter baumannii; gram-negative bacteria; polymyxins; antimetabolites; antivirulence drugs; outer membrane biogenesis; essential genes; iron uptake; lipopolysaccharide

Special Issue Information

Dear Colleagues,

Antimicrobial resistance (AMR) is one of the major challenges of this century. International organizations have been working to mitigate this phenomenon, and the first step in controlling it is to consider the issue within the One Health concept. In recent years, virulence has emerged as a growing threat in Gram-negative multi-drug-resistant pathogens. The association of AMR with virulence creates a perfect scenario for the success of these pathogens, whether by enabling their persistence in various environments or by making it difficult to achieve effective antibiotic treatment when they cause infections, among other factors. Therefore, it is important to assess the impact of this alliance within the One Health framework. The main focus of this Special Issue is AMR and virulence in Gram-negative bacteria across human and veterinary medicine, natural environments, the food industry, and agriculture.

Dr. Francesco Imperi
Guest Editor

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Keywords

  • virulence
  • Gram-negative
  • antimicrobial resistance
  • One Health

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Published Papers (5 papers)

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Research

12 pages, 652 KiB  
Article
Variable In Vitro Efficacy of Delafloxacin on Multidrug-Resistant Pseudomonas aeruginosa and the Detection of Delafloxacin Resistance Determinants
by András Kubicskó, Katalin Kamotsay, Péter Banczerowski, László Sipos, Dóra Szabó and Béla Kocsis
Antibiotics 2025, 14(6), 542; https://doi.org/10.3390/antibiotics14060542 (registering DOI) - 25 May 2025
Abstract
Background: In this study, molecular mechanisms contributing to delafloxacin resistance in Pseudomonas aeruginosa strains were investigated. Delafloxacin is a recently approved fluoroquinolone currently introduced to clinical applications. Methods: A total of 52 P. aeruginosa strains were collected from clinical isolates. Antimicrobial susceptibility testing [...] Read more.
Background: In this study, molecular mechanisms contributing to delafloxacin resistance in Pseudomonas aeruginosa strains were investigated. Delafloxacin is a recently approved fluoroquinolone currently introduced to clinical applications. Methods: A total of 52 P. aeruginosa strains were collected from clinical isolates. Antimicrobial susceptibility testing was performed via broth microdilution, and the minimum inhibitory concentration (MIC) values for ciprofloxacin, levofloxacin, delafloxacin, ceftazidime and imipenem were determined. Five delafloxacin-resistant P. aeruginosa strains were selected for whole-genome sequencing (WGS). Results: MIC50 values were determined, and the following results were obtained: ciprofloxacin 0.25 mg/L, levofloxacin 0.25 mg/L and delafloxacin 1 mg/L. All five selected strains showed both extended-spectrum beta-lactamase and carbapenemase production. WGS analysis of these strains determined the sequence types (STs), namely, ST235 (two strains), ST316 (two strains) and ST395. Several mutations in quinolone-resistance-determining regions (QRDRs) were detected in all five delafloxacin-resistant P. aeruginosa strains as follows: gyrA Thr83Ile and parC Ser87Leu mutations were present in all five strains, while parE Thr223Ala in ST235, Glu459Val in ST316 and Val200Met in ST395 were detected. MexAB-OprM and MexCD-OprJ efflux pumps were uniformly present in all delafloxacin-resistant P. aeruginosa strains. All strains of ST235 and ST316 carried blaNDM-1 in combination with other beta-lactamases. In our study, the in vitro efficacy of delafloxacin is inferior compared to previous fluoroquinolones based on MIC50 values; however, MIC values of delafloxacin ranged between 0.125 and 128 mg/L in our P. aeruginosa collection, and 21 out of 52 strains showed susceptibility to delafloxacin. Conclusions: Multiple QRDR mutations combined with several efflux pumps confer delafloxacin resistance in P. aeruginosa. Among the different detected multidrug-resistant P. aeruginosa strains in this study, we also report on an NDM-1 producing P. aeruginosa ST316 in Hungary. Full article
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10 pages, 767 KiB  
Article
Prevalence of Acinetobacter baumannii Multidrug Resistance in University Hospital Environment
by Francesco Foglia, Annalisa Ambrosino, Shahab Bashir, Emiliana Finamore, Carla Zannella, Giovanna Donnarumma, Anna De Filippis and Massimiliano Galdiero
Antibiotics 2025, 14(5), 490; https://doi.org/10.3390/antibiotics14050490 - 10 May 2025
Viewed by 301
Abstract
Background: Acinetobacter baumannii is a significant pathogen and a major contributor to healthcare-associated infections, particularly in intensive care units. Its high potential for developing multiple drug resistance (MDR) makes it a challenging pathogen to manage. This study investigates the prevalence and resistance [...] Read more.
Background: Acinetobacter baumannii is a significant pathogen and a major contributor to healthcare-associated infections, particularly in intensive care units. Its high potential for developing multiple drug resistance (MDR) makes it a challenging pathogen to manage. This study investigates the prevalence and resistance patterns of MDR A. baumannii isolates over a six-year period at a university hospital in Southern Italy. Objective: The aims of this study are to evaluate recent trends in the prevalence of MDR A. baumannii, analyze resistance patterns, and assess the impact of the antimicrobial diagnostic stewardship program implemented in 2018. Methods: This retrospective cohort study was conducted at the University Hospital of Campania “Luigi Vanvitelli” from 2018 to 2023. A total of 191 A. baumannii isolates from blood, urine, and wound samples were analyzed. Antimicrobial susceptibility testing was performed following EUCAST guidelines. The prevalence of MDR strains was assessed across three periods: pre-pandemic (2018–2019), during the pandemic (2020–2021), and post-pandemic (2022–2023) Results: Among the 191 isolates, 89.5% were classified as MDR. The highest number of isolates occurred in 2020, with blood cultures and urine samples increasing by 40.9% and 62.5%, respectively, while wound isolates decreased by 34.2%. The implementation of antimicrobial diagnostic stewardship programs correlated with a reduction in carbapenem resistance in 2020 and 2022. However, resistance to meropenem and colistin persisted. A 60.4% decline in total isolation from 2020 to 2023 suggests effective infection control measures. Conclusions: MDR A. baumannii remains a significant threat to healthcare. Although there have been slight reductions in resistance following antimicrobial stewardship interventions, persistent resistance to last-line antibiotics underscores the urgent need for alternative treatments, enhanced surveillance, and stricter infection control strategies. Full article
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13 pages, 249 KiB  
Article
Distribution of Fimbrial Genes and Their Association with Virulence and Levofloxacin Resistance/Extended-Spectrum Beta-Lactamase Production in Uropathogenic Escherichia coli
by Masao Mitsui, Takanori Sekito, Mai Maruhashi, Yuki Maruyama, Takehiro Iwata, Yusuke Tominaga, Satoshi Katayama, Shingo Nishimura, Kensuke Bekku, Motoo Araki, Hidetada Hirakawa and Takuya Sadahira
Antibiotics 2025, 14(5), 468; https://doi.org/10.3390/antibiotics14050468 - 6 May 2025
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Abstract
Background: Urinary tract infection (UTI) is predominantly caused by uropathogenic Escherichia coli (UPEC). Previous studies have reported that the fimbriae of UPEC are involved in virulence and antimicrobial resistance. We aimed to analyze the fimbrial gene profiles of UPEC and investigate the specificity [...] Read more.
Background: Urinary tract infection (UTI) is predominantly caused by uropathogenic Escherichia coli (UPEC). Previous studies have reported that the fimbriae of UPEC are involved in virulence and antimicrobial resistance. We aimed to analyze the fimbrial gene profiles of UPEC and investigate the specificity of these expressions in symptomatic UTI, urinary device use, and levofloxacin (LVFX) resistance/extended-spectrum beta-lactamase (ESBL) production. Methods: A total of 120 UPEC strains were isolated by urine culture between 2019 and 2023 at our institution. They were subjected to an antimicrobial susceptibility test and polymerase chain reaction (PCR) to identify 14 fimbrial genes and their association with clinical outcomes or antimicrobial resistance. Results: The prevalence of the papG2 gene was significantly higher in the symptomatic UTI group by multivariate analyses (OR 5.850, 95% CI 1.390–24.70, p = 0.016). The prevalence of the c2395 gene tended to be lower in the symptomatic UTI group with urinary devices (all p < 0.05). In LVFX-resistant UPEC strains from both the asymptomatic bacteriuria (ABU) and the symptomatic UTI group, the expression of the papEF, papG3, c2395, and yadN genes tended to be lower (all p < 0.05). Conclusion: The fimbrial genes of UPEC are associated with virulence and LVFX resistance, suggesting that even UPEC with fewer motility factors may be more likely to ascend the urinary tract in the presence of the urinary devices. These findings may enhance not only the understanding of the virulence of UPEC but also the management of UTI. Full article
15 pages, 2636 KiB  
Article
High-Risk Lineages of Hybrid Plasmids Carrying Virulence and Carbapenemase Genes
by Valeria V. Shapovalova, Polina S. Chulkova, Vladimir A. Ageevets, Varvara Nurmukanova, Irina V. Verentsova, Asya A. Girina, Irina N. Protasova, Victoria S. Bezbido, Victor I. Sergevnin, Irina V. Feldblum, Larisa G. Kudryavtseva, Sergey N. Sharafan, Vladislav V. Semerikov, Marina L. Babushkina, Inna R. Valiullina, Nikita S. Chumarev, Guzel S. Isaeva, Natalya A. Belyanina, Irina U. Shirokova, Tatiana M. Mrugova, Elena I. Belkova, Svetlana D. Artemuk, Aleksandra A. Meltser, Marina V. Smirnova, Tatyana N. Akkonen, Nataliya A. Golovshchikova, Oleg V. Goloshchapov, Alexey B. Chukhlovin, Lubov N. Popenko, Elena Y. Zenevich, Aleksandr A. Vlasov, Galina V. Mitroshina, Marina S. Bordacheva, Irina V. Ageevets, Ofeliia S. Sulian, Alisa A. Avdeeva, Vladimir V. Gostev, Irina A. Tsvetkova, Maria A. Yakunina, Ekaterina U. Vasileva, Alina D. Matsvay, Dmitry I. Danilov, Yulia A. Savochkina, German A. Shipulin and Sergey V. Sidorenkoadd Show full author list remove Hide full author list
Antibiotics 2024, 13(12), 1224; https://doi.org/10.3390/antibiotics13121224 - 17 Dec 2024
Cited by 1 | Viewed by 1421
Abstract
Background/Objectives: Carbapenem-resistant Enterobacterales (CRE) are a global health threat due to their high morbidity and mortality rates and limited treatment options. This study examines the plasmid-mediated transmission of virulence and antibiotic resistance determinants in carbapenem-resistant Klebsiella pneumoniae (Kpn) and Escherichia coli [...] Read more.
Background/Objectives: Carbapenem-resistant Enterobacterales (CRE) are a global health threat due to their high morbidity and mortality rates and limited treatment options. This study examines the plasmid-mediated transmission of virulence and antibiotic resistance determinants in carbapenem-resistant Klebsiella pneumoniae (Kpn) and Escherichia coli (E. coli) isolated from Russian hospitals. Methods: We performed short- and long-read whole-genome sequencing of 53 clinical isolates (48 Kpn and 5 E. coli) attributed to 15 genetic lineages and collected from 21 hospitals across nine Russian cities between 2016 and 2022. Results: The plasmid analysis identified 18 clusters that showed high concordance with replicon typing, with all clusters having a major replicon type. The majority of plasmids in the IncHI1B(pNDM-MAR)/IncFIB(pNDM-Mar)-like cluster (79.16%) carried both antibiotic resistance genes (e.g., blaNDM-1 and blaOXA-48) and virulence factors (VFs) such as siderophore genes. We hypothesized that hybrid plasmids could play a critical role in the dissemination of antibiotic resistance genes and VFs. Comparative analyses with global plasmid databases revealed high-risk lineages of hybrid plasmids that are predominantly spread throughout Russia at present. Conclusions: Our findings underscore the importance of monitoring plasmid backbones for clinical management, surveillance, and infection control activities. Full article
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21 pages, 1191 KiB  
Article
Tracking Multidrug Resistance in Gram-Negative Bacteria in Alexandria, Egypt (2020–2023): An Integrated Analysis of Patient Data and Diagnostic Tools
by Sascha D. Braun, Shahinda Rezk, Christian Brandt, Martin Reinicke, Celia Diezel, Elke Müller, Katrin Frankenfeld, Domenique Krähmer, Stefan Monecke and Ralf Ehricht
Antibiotics 2024, 13(12), 1185; https://doi.org/10.3390/antibiotics13121185 - 5 Dec 2024
Viewed by 1514
Abstract
Background: The rise in carbapenem-resistant Enterobacteriaceae (CRE) in Egypt, particularly in hospital settings, poses a significant public health challenge. This study aims to develop a combined epidemiological surveillance tool utilizing the Microreact online platform (version 269) and molecular microarray technology to track and [...] Read more.
Background: The rise in carbapenem-resistant Enterobacteriaceae (CRE) in Egypt, particularly in hospital settings, poses a significant public health challenge. This study aims to develop a combined epidemiological surveillance tool utilizing the Microreact online platform (version 269) and molecular microarray technology to track and analyze carbapenem-resistant Escherichia coli strains in Egypt. The objective is to integrate molecular diagnostics and real-time data visualization to better understand the spread and evolution of multidrug-resistant (MDR) bacteria. Methods: The study analyzed 43 E. coli isolates collected from Egyptian hospitals between 2020 and 2023. Nanopore sequencing and microarray analysis were used to identify carbapenemase genes and other resistance markers, whereas the VITEK2 system was employed for phenotypic antibiotic susceptibility testing. Microreact was used to visualize epidemiological data, mapping the geographic and temporal distribution of resistant strains. Results: We found that 72.09% of the isolates, predominantly from pediatric patients, carried the blaNDM-5 gene, while other carbapenemase genes, including blaOXA-48 and blaVIM, were also detected. The microarray method demonstrated 92.9% diagnostic sensitivity and 87.7% diagnostic specificity compared to whole-genome sequencing. Phenotypic resistance correlated strongly with next-generation sequencing (NGS) genotypic data, achieving 95.6% sensitivity and 95.2% specificity. Conclusions: This method establishes the utility of combining microarray technology, NGS and real-time data visualization for the surveillance of carbapenem-resistant Enterobacteriaceae, especially E. coli. The high concordance between genotypic and phenotypic data underscores the potential of DNA microarrays as a cost-effective alternative to whole-genome sequencing, especially in resource-limited settings. This integrated approach can enhance public health responses to MDR bacteria in Egypt. Full article
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