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Genomic Analysis of Antibiotics Resistance in Pathogens

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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: closed (31 March 2022) | Viewed by 41194

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Dr. Teresa V. Nogueira

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INIAV - National Institute for Agrarian and Veterinarian Research / cE3c - Centre for Ecology, Evolution and Environmental Changes, University of Lisbon, Lisbon, Portugal
Interests: bacterial genomics; microbiome dynamics; evolution
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Dear Colleagues,

The emergence of antibiotic-resistant pathogens currently poses a serious threat to public health and the economy. Due to antibiotic treatments in humans and in veterinary medicine, pathogenic bacteria are the most frequently exposed to unnatural doses of antibiotics and their selective effect.

In bacteria, resistance to antibiotics can be encoded on chromosomes, plasmids, or other mobile genetic elements. It can also result from mutations that lead to changes in the antibiotics’ affinity for their targets or in the antibiotics' ability to act on bacterial growth or death. The exposure of bacteria, bacterial populations, and microbial communities to antibiotics, at different concentrations, shapes their genomic dynamics, such as the mobilization and spreading of resistance determinants. It is essential to understand the dynamics and mobilization of the genes that encode antibiotic resistance, in human, animal, plant, and environmental microbiomes, through genomic and metagenomic approaches and bioinformatics analyses.

This Special Issue seeks manuscript submissions on the horizontal transfer of antibiotic-resistance genes, their dissemination and epidemiology, association with bacterial virulence, between bacterial genotypes and their phenotypes, or any related research topic.

Dr. Teresa V. Nogueira
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

antibiotic resistance
genome analysis
metagenome analysis
horizontal gene transfer
clinical microbiology
veterinary microbiology
superbugs

Published Papers (14 papers)

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Editorial

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3 pages, 196 KiB

Open AccessEditorial

Genomic Analysis of Antibiotics Resistance in Pathogens

by Teresa Nogueira

Antibiotics 2022, 11(8), 1013; https://doi.org/10.3390/antibiotics11081013 - 28 Jul 2022

Viewed by 1380

Abstract

The emergence of antibiotic-resistant pathogens currently represents a serious threat to public health and the economy worldwide [...] Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

Research

Jump to: Editorial, Review

23 pages, 2937 KiB

Open AccessArticle

Comparative Genomic Analysis Discloses Differential Distribution of Antibiotic Resistance Determinants between Worldwide Strains of the Emergent ST213 Genotype of Salmonella Typhimurium

by Elda Araceli Hernández-Díaz, Ma. Soledad Vázquez-Garcidueñas, Andrea Monserrat Negrete-Paz and Gerardo Vázquez-Marrufo

Antibiotics 2022, 11(7), 925; https://doi.org/10.3390/antibiotics11070925 - 9 Jul 2022

Cited by 3 | Viewed by 1951

Abstract

Salmonella enterica constitutes a global public health concern as one of the main etiological agents of human gastroenteritis. The Typhimurium serotype is frequently isolated from human, animal, food, and environmental samples, with its sequence type 19 (ST19) being the most widely distributed around the world as well as the founder genotype. The replacement of the ST19 genotype with the ST213 genotype that has multiple antibiotic resistance (MAR) in human and food samples was first observed in Mexico. The number of available genomes of ST213 strains in public databases indicates its fast worldwide dispersion, but its public health relevance is unknown. A comparative genomic analysis conducted as part of this research identified the presence of 44 genes, 34 plasmids, and five point mutations associated with antibiotic resistance, distributed across 220 genomes of ST213 strains, indicating the MAR phenotype. In general, the grouping pattern in correspondence to the presence/absence of genes/plasmids that confer antibiotic resistance cluster the genomes according to the geographical origin where the strain was isolated. Genetic determinants of antibiotic resistance group the genomes of North America (Canada, Mexico, USA) strains, and suggest a dispersion route to reach the United Kingdom and, from there, the rest of Europe, then Asia and Oceania. The results obtained here highlight the worldwide public health relevance of the ST213 genotype, which contains a great diversity of genetic elements associated with MAR. Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

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12 pages, 956 KiB

Open AccessArticle

Genomic Analysis of Two MDR Isolates of Salmonella enterica Serovar Infantis from a Spanish Hospital Bearing the bla_CTX-M-65 Gene with or without fosA3 in pESI-like Plasmids

by Xenia Vázquez, Javier Fernández, Jesús Rodríguez-Lozano, Jorge Calvo, Rosaura Rodicio and M. Rosario Rodicio

Antibiotics 2022, 11(6), 786; https://doi.org/10.3390/antibiotics11060786 - 9 Jun 2022

Cited by 7 | Viewed by 2350

Abstract

Salmonella enterica serovar Infantis (S. Infantis) is a broiler-associated pathogen which ranks in the fourth position as a cause of human salmonellosis in the European Union. Here, we report a comparative genomic analysis of two clinical S. Infantis isolates recovered in Spain from children who just returned from Peru. The isolates were selected on the basis of resistance to cefotaxime, one of the antibiotics of choice for treatment of S. enterica infections. Antimicrobial susceptibility testing demonstrated that they were resistant to eight classes of antimicrobial agents: penicillins, cephalosporins, phenicols, aminoglycosides, tetracyclines, inhibitors of folate synthesis, (fluoro)quinolones and nitrofurans, and one of them was also resistant to fosfomycin. As shown by whole-genome sequence analysis, each isolate carried a pESI-like megaplasmid of ca. 300 kb harboring multiple resistance genes [bla_CTX-M-65, aph(4)-Ia, aac(3)-IVa, aph(3′)-Ia, floR, dfrA14, sul1, tet(A), aadA1 ± fosA3], as well as genes for resistance to heavy metals and disinfectants (mer, ars and qacEΔ1). These genes were distributed in two complex regions, separated by DNA belonging to the plasmid backbone, and associated with a wealth of transposable elements. The two isolates had a D87Y amino acid substitution in the GyrA protein, and truncated variants of the nitroreductase genes nfsA and nsfB, accounting for chromosomally encoded resistances to nalidixic acid and nitrofurantoin, respectively. The two S. Infantis isolates were assigned to sequence type ST32 by in silico multilocus sequence typing (MLST). Phylogenetic analysis revealed that they were closely related, differing only by 12 SNPs, although they were recovered from different children two years apart. They were also genetically similar to bla_CTX-M-65-positive ± fosA3 isolates obtained from humans and along the poultry production chain in the USA, South America, as well as from humans in several European countries, usually associated with a travel history to America. However, this is the first time that the S. Infantis bla_CTX-M-65 ± fosA3 MDR clone has been reported in Spain. Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

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24 pages, 4302 KiB

Open AccessArticle

Are Virulence and Antibiotic Resistance Genes Linked? A Comprehensive Analysis of Bacterial Chromosomes and Plasmids

by Helena Darmancier, Célia P. F. Domingues, João S. Rebelo, Ana Amaro, Francisco Dionísio, Joël Pothier, Octávio Serra and Teresa Nogueira

Antibiotics 2022, 11(6), 706; https://doi.org/10.3390/antibiotics11060706 - 24 May 2022

Cited by 13 | Viewed by 5384

Abstract

Although pathogenic bacteria are the targets of antibiotics, these drugs also affect hundreds of commensal or mutualistic species. Moreover, the use of antibiotics is not only restricted to the treatment of infections but is also largely applied in agriculture and in prophylaxis. During this work, we tested the hypothesis that there is a correlation between the number and the genomic location of antibiotic resistance (AR) genes and virulence factor (VF) genes. We performed a comprehensive study of 16,632 reference bacterial genomes in which we identified and counted all orthologues of AR and VF genes in each of the locations: chromosomes, plasmids, or in both locations of the same genome. We found that, on a global scale, no correlation emerges. However, some categories of AR and VF genes co-occur preferentially, and in the mobilome, which supports the hypothesis that some bacterial pathogens are under selective pressure to be resistant to specific antibiotics, a fact that can jeopardize antimicrobial therapy for some human-threatening diseases. Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

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18 pages, 2730 KiB

Open AccessArticle

Genomic Analysis of Multidrug-Resistant Hypervirulent (Hypermucoviscous) Klebsiella pneumoniae Strain Lacking the Hypermucoviscous Regulators (rmpA/rmpA2)

by Hisham N. Altayb, Hana S. Elbadawi, Othman Baothman, Imran Kazmi, Faisal A. Alzahrani, Muhammad Shahid Nadeem, Salman Hosawi and Kamel Chaieb

Antibiotics 2022, 11(5), 596; https://doi.org/10.3390/antibiotics11050596 - 28 Apr 2022

Cited by 16 | Viewed by 2671

Abstract

Hypervirulent K. pneumoniae (hvKP) strains possess distinct characteristics such as hypermucoviscosity, unique serotypes, and virulence factors associated with high pathogenicity. To better understand the genomic characteristics and virulence profile of the isolated hvKP strain, genomic data were compared to the genomes of the hypervirulent and typical K. pneumoniae strains. The K. pneumoniae strain was isolated from a patient with a recurrent urinary tract infection, and then the string test was used for the detection of the hypermucoviscosity phenotype. Whole-genome sequencing was conducted using Illumina, and bioinformatics analysis was performed for the prediction of the isolate resistome, virulome, and phylogenetic analysis. The isolate was identified as hypermucoviscous, type 2 (K2) capsular polysaccharide, ST14, and multidrug-resistant (MDR), showing resistance to ciprofloxacin, ceftazidime, cefotaxime, trimethoprim-sulfamethoxazole, cephalexin, and nitrofurantoin. The isolate possessed four antimicrobial resistance plasmids (pKPN3-307_type B, pECW602, pMDR, and p3K157) that carried antimicrobial resistance genes (ARGs) (bla_OXA-1,bla_CTX-M-15, sul2, APH(3″)-Ib, APH(6)-Id, and AAC(6′)-Ib-cr6). Moreover, two chromosomally mediated ARGs (fosA6 and SHV-28) were identified. Virulome prediction revealed the presence of 19 fimbrial proteins, one aerobactin (iutA) and two salmochelin (iroE and iroN). Four secretion systems (T6SS-I (13), T6SS-II (9), T6SS-III (12), and Sci-I T6SS (1)) were identified. Interestingly, the isolate lacked the known hypermucoviscous regulators (rmpA/rmpA2) but showed the presence of other RcsAB capsule regulators (rcsA and rcsB). This study documented the presence of a rare MDR hvKP with hypermucoviscous regulators and lacking the common capsule regulators, which needs more focus to highlight their epidemiological role. Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

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12 pages, 1254 KiB

Open AccessArticle

Alternative Pathways to Ciprofloxacin Resistance in Neisseria gonorrhoeae: An In Vitro Study of the WHO-P and WHO-F Reference Strains

by Natalia González, Saïd Abdellati, Irith De Baetselier, Jolein Gyonne Elise Laumen, Christophe Van Dijck, Tessa de Block, Chris Kenyon and Sheeba Santhini Manoharan-Basil

Antibiotics 2022, 11(4), 499; https://doi.org/10.3390/antibiotics11040499 - 8 Apr 2022

Cited by 6 | Viewed by 1907

Abstract

Emerging resistance to ceftriaxone and azithromycin has led to renewed interest in using ciprofloxacin to treat Neisseria gonorrhoeae. This could lead to the rapid emergence and spread of ciprofloxacin resistance. Previous studies investigating the emergence of fluoroquinolone resistance have been limited to a single strain of N. gonorrhoeae. It is unknown if different genetic backgrounds affect the evolution of fluoroquinolone resistance in N. gonorrhoeae, as has been shown in other bacterial species. This study evaluated the molecular pathways leading to ciprofloxacin resistance in two reference strains of N.gonorrhoeae—WHO-F and WHO-P. Three clones of each of the two strains of N.gonorrhoeae were evolved in the presence of ciprofloxacin, and isolates from different time points were whole-genome sequenced. We found evidence of strain-specific differences in the emergence of ciprofloxacin resistance. Two out of three clones from WHO-P followed the canonical pathway to resistance proceeding via substitutions in GyrA-S91F, GyrA-D95N and ParC. None of the three WHO-F clones followed this pathway. In addition, mutations in gyrB, uvrA and rne frequently occurred in WHO-F clones, whereas mutations in yhgF, porB and potA occurred in WHO-P. Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

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16 pages, 2572 KiB

Open AccessArticle

Comparative Genomic Analysis of a Panton–Valentine Leukocidin-Positive ST22 Community-Acquired Methicillin-Resistant Staphylococcus aureus from Pakistan

by Nimat Ullah, Samavi Nasir, Zaara Ishaq, Farha Anwer, Tanzeela Raza, Moazur Rahman, Abdulrahman Alshammari, Metab Alharbi, Taeok Bae, Abdur Rahman and Amjad Ali

Antibiotics 2022, 11(4), 496; https://doi.org/10.3390/antibiotics11040496 - 8 Apr 2022

Cited by 6 | Viewed by 2314

Abstract

Staphylococcus aureus (S. aureus) ST22 is considered a clinically important clone because an epidemic strain EMRSA-15 belongs to ST22, and several outbreaks of this clone have been documented worldwide. We performed genomic analysis of an S. aureus strain Lr2 ST22 from Pakistan and determined comparative analysis with other ST22 strains. The genomic data show that Lr2 belongs to spa-type t2986 and harbors staphylococcal cassette chromosome mec (SCCmec) type IVa(2B), one complete plasmid, and seven prophages or prophage-like elements. The strain harbors several prophage-associated virulence factors, including Panton–Valentine leukocidin (PVL) and toxic shock syndrome toxin (TSST). The single nucleotide polymorphism (SNPs)-based phylogenetic relationship inferred from whole genome and core genome revealed that strain Lr2 exhibits the nearest identities to a South African community-acquired methicillin-resistant S. aureus (CA-MRSA) ST22 strain and makes a separate clade with an Indian CA-MRSA ST22 strain. Although most ST22 strains carry blaZ, mecA, and mutations in gyrA, the Lr2 strain does not have the blaZ gene but, unlike other ST22 strains, carries the antibiotic resistance genes erm(C) and aac(6′)-Ie-aph(2″)-Ia. Among ST22 strains analyzed, only the strain Lr2 possesses both PVL and TSST genes. The functional annotation of genes unique to Lr2 revealed that mobilome is the third-largest Cluster of Orthologous Genes (COGs) category, which encodes genes associated with prophages and transposons. This possibly makes methicillin-resistant S. aureus (MRSA) Lr2 ST22 strain highly virulent, and this study would improve the knowledge of MRSA ST22 strains in Pakistan. However, further studies are needed on a large collection of MRSA to comprehend the genomic epidemiology and evolution of this clone in Pakistan. Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

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11 pages, 323 KiB

Open AccessArticle

First Description of Ceftazidime/Avibactam Resistance in a ST13 KPC-70-Producing Klebsiella pneumoniae Strain from Portugal

by Gabriel Mendes, João F. Ramalho, Ana Bruschy-Fonseca, Luís Lito, Aida Duarte, José Melo-Cristino and Cátia Caneiras

Antibiotics 2022, 11(2), 167; https://doi.org/10.3390/antibiotics11020167 - 27 Jan 2022

Cited by 11 | Viewed by 2875

Abstract

The combination of ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor with activity against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales. Emerging cases caused by CZA-resistant strains that produce variants of KPC genes have already been reported worldwide. However, to the best of our knowledge, no CZA-resistant strains were reported in Portugal. In September 2019, a K. pneumoniae CZA-resistant strain was collected from ascitic fluid at a surgery ward of a tertiary University Hospital Center in Lisboa, Portugal. The strain was resistant to ceftazidime/avibactam, as well as to ceftazidime, cefoxitin, gentamicin, amoxicillin/clavulanic acid, and ertapenem, being susceptible to imipenem and tigecycline. A hypermucoviscosity phenotype was confirmed by string test. Whole-genome sequencing (WGS) analysis revealed the presence of an ST13 KPC70-producing K. pneumoniae, a KPC-3 variant, differing in two amino-acid substitutions (D179Y and T263A). The D179Y mutation in the KPC Ω-loop region is the most common amino-acid substitution in KPC-2 and KPC-3, further leading to CZA resistance. The second mutation causes a KPC-70 variant in which threonine replaces alanine (T263A). The CZA-resistant strain showed the capsular locus KL3 and antigen locus O1v2. Other important virulence factors were identified: fimbrial adhesins type 1 and type 3, as well as the cluster of iron uptake systems aerobactin, enterobactin, salmochelin, and yersiniabactin included in integrative conjugative element 10 (ICEKp10) with the genotoxin colibactin cluster. Herein, we report the molecular characterization of the first hypervirulent CZA-resistant ST13 KPC-70-producing K. pneumoniae strain in Portugal. The emergence of CZA-resistant strains might pose a serious threat to public health and suggests an urgent need for enhanced clinical awareness and epidemiologic surveillance. Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

16 pages, 3758 KiB

Open AccessArticle

Colistin and Carbapenem-Resistant Acinetobacter baumannii Aci46 in Thailand: Genome Analysis and Antibiotic Resistance Profiling

by Nalumon Thadtapong, Soraya Chaturongakul, Sunhapas Soodvilai and Padungsri Dubbs

Antibiotics 2021, 10(9), 1054; https://doi.org/10.3390/antibiotics10091054 - 30 Aug 2021

Cited by 10 | Viewed by 3628

Abstract

Resistance to the last-line antibiotics against invasive Gram-negative bacterial infection is a rising concern in public health. Multidrug resistant (MDR) Acinetobacter baumannii Aci46 can resist colistin and carbapenems with a minimum inhibitory concentration of 512 µg/mL as determined by microdilution method and shows no zone of inhibition by disk diffusion method. These phenotypic characteristics prompted us to further investigate the genotypic characteristics of Aci46. Next generation sequencing was applied in this study to obtain whole genome data. We determined that Aci46 belongs to Pasture ST2 and is phylogenetically clustered with international clone (IC) II as the predominant strain in Thailand. Interestingly, Aci46 is identical to Oxford ST1962 that previously has never been isolated in Thailand. Two plasmids were identified (pAci46a and pAci46b), neither of which harbors any antibiotic resistance genes but pAci46a carries a conjugational system (type 4 secretion system or T4SS). Comparative genomics with other polymyxin and carbapenem-resistant A. baumannii strains (AC30 and R14) identified shared features such as CzcCBA, encoding a cobalt/zinc/cadmium efflux RND transporter, as well as a drug transporter with a possible role in colistin and/or carbapenem resistance in A. baumannii. Single nucleotide polymorphism (SNP) analyses against MDR ACICU strain showed three novel mutations i.e., Glu229Asp, Pro200Leu, and Ala138Thr, in the polymyxin resistance component, PmrB. Overall, this study focused on Aci46 whole genome data analysis, its correlation with antibiotic resistance phenotypes, and the presence of potential virulence associated factors. Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

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10 pages, 799 KiB

Open AccessArticle

Role of dipA and pilD in Francisella tularensis Susceptibility to Resazurin

by Kendall Souder, Emma J. Beatty, Siena C. McGovern, Michael Whaby, Emily Young, Jacob Pancake, Daron Weekley, Justin Rice, Donald A. Primerano, James Denvir, Joseph Horzempa and Deanna M. Schmitt

Antibiotics 2021, 10(8), 992; https://doi.org/10.3390/antibiotics10080992 - 17 Aug 2021

Cited by 2 | Viewed by 2347

Abstract

The phenoxazine dye resazurin exhibits bactericidal activity against the Gram-negative pathogens Francisella tularensis and Neisseria gonorrhoeae. One resazurin derivative, resorufin pentyl ether, significantly reduces vaginal colonization by Neisseria gonorrhoeae in a mouse model of infection. The narrow spectrum of bacteria susceptible to resazurin and its derivatives suggests these compounds have a novel mode of action. To identify potential targets of resazurin and mechanisms of resistance, we isolated mutants of F. tularensis subsp. holarctica live vaccine strain (LVS) exhibiting reduced susceptibility to resazurin and performed whole genome sequencing. The genes pilD (FTL_0959) and dipA (FTL_1306) were mutated in half of the 46 resazurin-resistant (RZR) strains sequenced. Complementation of select RZR LVS isolates with wild-type dipA or pilD partially restored sensitivity to resazurin. To further characterize the role of dipA and pilD in resazurin susceptibility, a dipA deletion mutant, ΔdipA, and pilD disruption mutant, FTL_0959d, were generated. Both mutants were less sensitive to killing by resazurin compared to wild-type LVS with phenotypes similar to the spontaneous resazurin-resistant mutants. This study identified a novel role for two genes dipA and pilD in F. tularensis susceptibility to resazurin. Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

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16 pages, 2392 KiB

Open AccessArticle

Co-Existence of Certain ESBLs, MBLs and Plasmid Mediated Quinolone Resistance Genes among MDR E. coli Isolated from Different Clinical Specimens in Egypt

by Salwa Mahmoud Masoud, Rehab Mahmoud Abd El-Baky, Sherine A. Aly and Reham Ali Ibrahem

Antibiotics 2021, 10(7), 835; https://doi.org/10.3390/antibiotics10070835 - 9 Jul 2021

Cited by 21 | Viewed by 3246

Abstract

The emergence of multi-drug resistant (MDR) strains and even pan drug resistant (PDR) strains is alarming. In this study, we studied the resistance pattern of E. coli pathogens recovered from patients with different infections in different hospitals in Minia, Egypt and the co-existence of different resistance determinants. E. coli was the most prevalent among patients suffering from urinary tract infections (62%), while they were the least isolated from eye infections (10%). High prevalence of MDR isolates was found (73%) associated with high ESBLs and MBLs production (89.4% and 64.8%, respectively). bla_TEM (80%) and bla_NDM (43%) were the most frequent ESBL and MBL, respectively. None of the isolates harbored bla_KPC and bla_OXA-48 carbapenemase like genes. Also, the fluoroquinolone modifying enzyme gene aac-(6′)-Ib-cr was detected in 25.2% of the isolates. More than one gene was found in 81% of the isolates. Azithromycin was one of the most effective antibiotics against MDR E. coli pathogens. The high MAR index of the isolates and the high prevalence of resistance genes, indicates an important public health concern and high-risk communities where antibiotics are abused. Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

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15 pages, 2660 KiB

Open AccessArticle

Effect of Titanium Dioxide Nanoparticles on the Expression of Efflux Pump and Quorum-Sensing Genes in MDR Pseudomonas aeruginosa Isolates

by Fatma Y. Ahmed, Usama Farghaly Aly, Rehab Mahmoud Abd El-Baky and Nancy G. F. M. Waly

Antibiotics 2021, 10(6), 625; https://doi.org/10.3390/antibiotics10060625 - 24 May 2021

Cited by 20 | Viewed by 2852

Abstract

Most of the infections caused by multi-drug resistant (MDR) P. aeruginosa strains are extremely difficult to be treated with conventional antibiotics. Biofilm formation and efflux pumps are recognized as the major antibiotic resistance mechanisms in MDR P. aeruginosa. Biofilm formation by P. aeruginosa depends mainly on the cell-to-cell communication quorum-sensing (QS) systems. Titanium dioxide nanoparticles (TDN) have been used as antimicrobial agents against several microorganisms but have not been reported as an anti-QS agent. This study aims to evaluate the impact of titanium dioxide nanoparticles (TDN) on QS and efflux pump genes expression in MDR P. aeruginosa isolates. The antimicrobial susceptibility of 25 P. aeruginosa isolates were performed by Kirby–Bauer disc diffusion. Titanium dioxide nanoparticles (TDN) were prepared by the sol gel method and characterized by different techniques (DLS, HR-TEM, XRD, and FTIR). The expression of efflux pumps in the MDR isolates was detected by the determination of MICs of different antibiotics in the presence and absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP). Biofilm formation and the antibiofilm activity of TDN were determined using the tissue culture plate method. The effects of TDN on the expression of QS genes and efflux pump genes were tested using real-time polymerase chain reaction (RT-PCR). The average size of the TDNs was 64.77 nm. It was found that TDN showed a significant reduction in biofilm formation (96%) and represented superior antibacterial activity against P. aeruginosa strains in comparison to titanium dioxide powder. In addition, the use of TDN alone or in combination with antibiotics resulted in significant downregulation of the efflux pump genes (MexY, MexB, MexA) and QS-regulated genes (lasR, lasI, rhll, rhlR, pqsA, pqsR) in comparison to the untreated isolate. TDN can increase the therapeutic efficacy of traditional antibiotics by affecting efflux pump expression and quorum-sensing genes controlling biofilm production. Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

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19 pages, 5614 KiB

Open AccessArticle

Pan-Resistome Insights into the Multidrug Resistance of Acinetobacter baumannii

by Diego Lucas Neres Rodrigues, Francielly Morais-Rodrigues, Raquel Hurtado, Roselane Gonçalves dos Santos, Daniela Camargos Costa, Debmalya Barh, Preetam Ghosh, Khalid J. Alzahrani, Siomar Castro Soares, Rommel Ramos, Aristóteles Góes-Neto, Vasco Azevedo and Flávia Figueira Aburjaile

Antibiotics 2021, 10(5), 596; https://doi.org/10.3390/antibiotics10050596 - 18 May 2021

Cited by 11 | Viewed by 3927

Abstract

Acinetobacter baumannii is an important Gram-negative opportunistic pathogen that is responsible for many nosocomial infections. This etiologic agent has acquired, over the years, multiple mechanisms of resistance to a wide range of antimicrobials and the ability to survive in different environments. In this context, our study aims to elucidate the resistome from the A. baumannii strains based on phylogenetic, phylogenomic, and comparative genomics analyses. In silico analysis of the complete genomes of A. baumannii strains was carried out to identify genes involved in the resistance mechanisms and the phylogenetic relationships and grouping of the strains based on the sequence type. The presence of genomic islands containing most of the resistance gene repertoire indicated high genomic plasticity, which probably enabled the acquisition of resistance genes and the formation of a robust resistome. A. baumannii displayed an open pan-genome and revealed a still constant genetic permutation among their strains. Furthermore, the resistance genes suggest a specific profile within the species throughout its evolutionary history. Moreover, the current study performed screening and characterization of the main genes present in the resistome, which can be used in applied research to develop new therapeutic methods to control this important bacterial pathogen. Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

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Review

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7 pages, 245 KiB

Open AccessReview

Genetic Determinants of Tigecycline Resistance in Mycobacteroides abscessus

by Hien Fuh Ng and Yun Fong Ngeow

Antibiotics 2022, 11(5), 572; https://doi.org/10.3390/antibiotics11050572 - 25 Apr 2022

Cited by 5 | Viewed by 2038

Abstract

Mycobacteroides abscessus (formerly Mycobacterium abscessus) is a clinically important, rapid-growing non-tuberculous mycobacterium notoriously known for its multidrug-resistance phenotype. The intrinsic resistance of M. abscessus towards first- and second-generation tetracyclines is mainly due to the over-expression of a tetracycline-degrading enzyme known as MabTetX (MAB_1496c). Tigecycline, a third-generation tetracycline, is a poor substrate for the MabTetX and does not induce the expression of this enzyme. Although tigecycline-resistant strains of M. abscessus have been documented in different parts of the world, their resistance determinants remain largely elusive. Recent work on tigecycline resistance or reduced susceptibility in M. abscessus revealed the involvement of the gene MAB_3508c which encodes the transcriptional activator WhiB7, as well as mutations in the sigH-rshA genes which control heat shock and oxidative-stress responses. The deletion of whiB7 has been observed to cause a 4-fold decrease in the minimum inhibitory concentration of tigecycline. In the absence of environmental stress, the SigH sigma factor (MAB_3543c) interacts with and is inhibited by the anti-sigma factor RshA (MAB_3542c). The disruption of the SigH-RshA interaction resulting from mutations and the subsequent up-regulation of SigH have been hypothesized to lead to tigecycline resistance in M. abscessus. In this review, the evidence for different genetic determinants reported to be linked to tigecycline resistance in M. abscessus was examined and discussed. Full article

(This article belongs to the Special Issue Genomic Analysis of Antibiotics Resistance in Pathogens)

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