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  1. Whole-genome analysis of an extensively drug-resistant clinical isolate of Acinetobacter baumannii AC12: insights into the mechanisms of resistance of an ST195 clone from Malaysia
    Lean SS, Yeo CC, Suhaili Z, Thong KL
    Int J Antimicrob Agents, 2015 Feb;45(2):178-82.
    PMID: 25481460 DOI: 10.1016/j.ijantimicag.2014.10.015
    Acinetobacter baumannii has emerged as an important nosocomial pathogen owing to its increasing resistance to most, if not all, antibiotics in clinical use. We recently reported the occurrence of extensively drug-resistant (XDR) A. baumannii isolates in a Malaysian tertiary hospital. The genome of one of these XDR isolates (A. baumannii AC12) was completely sequenced and comparative genome analyses were performed to elucidate the genetic basis of its antimicrobial resistance. The A. baumannii AC12 genome consists of a 3.8 Mbp circular chromosome and an 8731 bp cryptic plasmid, pAC12. It belongs to the ST195 lineage and is most closely related to A. baumannii BJAB0715 as well as other strains of the international clone III (IC-III) group. Two antibiotic resistance islands (RIs), designated AC12-RI1 and AC12-RI2, were found in the AC12 chromosome along with a 7 kb Tn1548::armA island conferring resistance to aminoglycosides and macrolides. The 22.8 kb AC12-RI1 interrupts the comM gene and harbours the carbapenem resistance gene blaOXA-23 flanked by ISAba1 within a Tn2006-like structure. AC12-RI1 also harbours resistance determinants for aminoglycosides, tetracyclines and sulphonamides. The 10.3 kb IS26-flanked AC12-RI2 is a derivative of AbGRI2-1, containing aphA1b and blaTEM genes (conferring aminoglycoside and β-lactam resistance, respectively). The presence of numerous genes mediating resistance to various antibiotics in novel RI structures as well as other genes encoding drug transporters and efflux pumps in A. baumannii AC12 most likely contributed to its XDR characteristics.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  2. Transcriptome analysis of Burkholderia pseudomallei SCV reveals an association with virulence, stress resistance and intracellular persistence
    Al-Maleki AR, Vellasamy KM, Mariappan V, Venkatraman G, Tay ST, Vadivelu J
    Genomics, 2020 01;112(1):501-512.
    PMID: 30980902 DOI: 10.1016/j.ygeno.2019.04.002
    Differences in expression of potential virulence and survival genes were associated with B. pseudomallei colony morphology variants. Microarray was used to investigate B. pseudomallei transcriptome alterations among the wild type and small colony variant (SCV) pre- and post-exposed to A549 cells. SCV pre- and post-exposed have lower metabolic requirements and consume lesser energy than the wild type pre- and post-exposed to A549. However, both the wild type and SCV limit their metabolic activities post- infection of A549 cells and this is indicated by the down-regulation of genes implicated in the metabolism of amino acids, carbohydrate, lipid, and other amino acids. Many well-known virulence and survival factors, including T3SS, fimbriae, capsular polysaccharides and stress response were up-regulated in both the wild type and SCV pre- and post-exposed to A549 cells. Microarray analysis demonstrated essential differences in bacterial response associated with virulence and survival pre- and post-exposed to A549 cells.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  3. Fulltext The role of interspecies recombination in the evolution of antibiotic-resistant pneumococci
    D'Aeth JC, van der Linden MP, McGee L, de Lencastre H, Turner P, Song JH, et al.
    Elife, 2021 Jul 14;10.
    PMID: 34259624 DOI: 10.7554/eLife.67113
    Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci by interspecies homologous recombinations, and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant S. pneumoniae lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn916-type and Tn1207.1-type elements, conferring tetracycline and macrolide resistance, respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking homologous arms. Phylodynamic analysis of the most commonly sampled Tn1207.1-type insertion in PMEN9, originating from a commensal and disrupting a competence gene, suggested its expansion across Germany was driven by a high ratio of macrolide-to-β-lactam consumption. Hence, selection from antibiotic consumption was sufficient for these atypically large recombinations to overcome species boundaries across the pneumococcal chromosome.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  4. The role of artificial intelligence in the battle against antimicrobial-resistant bacteria
    Lau HJ, Lim CH, Foo SC, Tan HS
    Curr Genet, 2021 Jun;67(3):421-429.
    PMID: 33585980 DOI: 10.1007/s00294-021-01156-5
    Antimicrobial resistance (AMR) in bacteria is a global health crisis due to the rapid emergence of multidrug-resistant bacteria and the lengthy development of new antimicrobials. In light of this, artificial intelligence in the form of machine learning has been viewed as a potential counter to delay the spread of AMR. With the aid of AI, there are possibilities to predict and identify AMR in bacteria efficiently. Furthermore, a combination of machine learning algorithms and lab testing can help to accelerate the process of discovering new antimicrobials. To date, many machine learning algorithms for antimicrobial-resistance discovery had been created and vigorously validated. Most of these algorithms produced accurate results and outperformed the traditional methods which relied on sequence comparison within a database. This mini-review will provide an updated overview of antimicrobial design workflow using the latest machine-learning antimicrobial discovery algorithms in the last 5 years. With this review, we hope to improve upon the current AMR identification and antimicrobial development techniques by introducing the use of AI into the mix, including how the algorithms could be made more effective.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  5. Fulltext The challenges of designing a benchmark strategy for bioinformatics pipelines in the identification of antimicrobial resistance determinants using next generation sequencing technologies
    Angers-Loustau A, Petrillo M, Bengtsson-Palme J, Berendonk T, Blais B, Chan KG, et al.
    F1000Res, 2018;7.
    PMID: 30026930 DOI: 10.12688/f1000research.14509.2
    Next-Generation Sequencing (NGS) technologies are expected to play a crucial role in the surveillance of infectious diseases, with their unprecedented capabilities for the characterisation of genetic information underlying the virulence and antimicrobial resistance (AMR) properties of microorganisms.  In the implementation of any novel technology for regulatory purposes, important considerations such as harmonisation, validation and quality assurance need to be addressed.  NGS technologies pose unique challenges in these regards, in part due to their reliance on bioinformatics for the processing and proper interpretation of the data produced.  Well-designed benchmark resources are thus needed to evaluate, validate and ensure continued quality control over the bioinformatics component of the process.  This concept was explored as part of a workshop on "Next-generation sequencing technologies and antimicrobial resistance" held October 4-5 2017.   Challenges involved in the development of such a benchmark resource, with a specific focus on identifying the molecular determinants of AMR, were identified. For each of the challenges, sets of unsolved questions that will need to be tackled for them to be properly addressed were compiled. These take into consideration the requirement for monitoring of AMR bacteria in humans, animals, food and the environment, which is aligned with the principles of a "One Health" approach.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  6. Fulltext Stenotrophomonas maltophilia in Malaysia: molecular epidemiology and trimethoprim-sulfamethoxazole resistance
    Neela V, Rankouhi SZ, van Belkum A, Goering RV, Awang R
    Int J Infect Dis, 2012 Aug;16(8):e603-7.
    PMID: 22698885 DOI: 10.1016/j.ijid.2012.04.004
    Stenotrophomonas maltophilia is a recently identified nosocomial pathogen in Malaysia. Despite limited pathogenicity, its rate of isolation has increased in recent years. The aim of this study was to investigate the antibiotic susceptibility patterns, antibiotic resistance determinants, and the epidemiology of S. maltophilia at the largest tertiary care hospital in Malaysia.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  7. Speciation and antimicrobial resistance of Enterococci isolated from recreational beaches in Malaysia
    Dada AC, Ahmad A, Usup G, Heng LY
    Environ Monit Assess, 2013 Feb;185(2):1583-99.
    PMID: 22592782 DOI: 10.1007/s10661-012-2653-6
    We report the first study on the occurrence of antibiotic-resistant enterococci in coastal bathing waters in Malaysia. One hundred and sixty-five enterococci isolates recovered from two popular recreational beaches in Malaysia were speciated and screened for antibiotic resistance to a total of eight antibiotics. Prevalence of Enterococcus faecalis and Enterococcus faecium was highest in both beaches. E. faecalis/E. faecium ratio was 0.384:1 and 0.375:1, respectively, for isolates from Port Dickson (PD) and Bagan Lalang (BL). Analysis of Fisher's exact test showed that association of prevalence of E. faecalis and E. faecium with considered locations was not statistically significant (p < 0.05). Chi-square test revealed significant differences (χ(2) = 82.630, df = 20, p < 0.001) in the frequency of occurrence of enterococci isolates from the considered sites. Resistance was highest to nalidixic acid (94.84 %) and least for chloramphenicol (8.38 %). One-way ANOVA using Tukey-Kramer multiple comparison test showed that resistance to ampicillin was higher in PD beach isolates than BL isolates and the difference was extremely statistically significant (p < 0.0001). Frequency of occurrence of multiple antibiotic resistance (MAR) isolates were higher for PD beach water (64.29 %) as compared to BL beach water (13.51 %), while MAR indices ranged between 0.198 and 0.48. The results suggest that samples from Port Dickson may contain MAR bacteria and that this could be due to high-risk faecal contamination from sewage discharge pipes that drain into the sea water.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  8. Fulltext Serotypes & penicillin susceptibility of Streptococcus pneumoniae isolated from children admitted to a tertiary teaching hospital in Malaysia
    Subramaniam P, Jabar KA, Kee BP, Chong CW, Nathan AM, de Bruyne J, et al.
    Indian J Med Res, 2018 Aug;148(2):225-231.
    PMID: 30381546 DOI: 10.4103/ijmr.IJMR_1987_16
    Background & objectives: Streptococcus pneumoniae: (pneumococcus) is a highly invasive extracellular pathogen that causes diseases such as pneumonia, otitis media and meningitis. This study was undertaken to determine the serotype diversity and penicillin susceptibility of S. pneumoniae isolated from paediatric patients in a tertiary teaching hospital in Malaysia.

    Methods: A total of 125 clinical isolates collected from January 2013 to May 2015 were serotyped using seven sequential multiplex polymerase chain reactions. The susceptibility of these isolates to penicillin was also investigated.

    Results: Serotypes detected among the isolates were serotypes 3, 6A/B, 6C, 11/A/D/F, 15A/F, 19A, 19F, 23A, 23F, 34. Serotypes 19F and 6A/B were the most prevalent serotypes detected. Most of the S. pneumoniae were isolated from nasopharyngeal samples of children below five years of age. Majority of the isolates were penicillin susceptible. Only 5.6 per cent of the isolates were non-susceptible to penicillin, mostly of serotype 19F.

    Interpretation & conclusions: Our study revealed the distribution of various serotypes in S. pneumoniae isolates obtained from children in a teaching hospital at Kuala Lumpur, Malaysia and decreasing rates of penicillin resistance among them. The shifts in serotypes and susceptibility to penicillin from time to time have been observed. Continuous monitoring and surveillance are pivotal for better infection control and management of pneumococcal infections among children.

    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  9. Plant genetic transformation efficiency of selected Malaysian rice based on selectable marker gene (hptII)
    Htwe NN, Ling HC, Zaman FQ, Maziah M
    Pak J Biol Sci, 2014 Apr;17(4):472-81.
    PMID: 25911833
    Rice is one of the most important cereal crops with great potential for biotechnology progress. In transformation method, antibiotic resistance genes are routinely used as powerful markers for selecting transformed cells from surrounding non-transformed cells. In this study, the toxicity level of hygromycin was optimized for two selected mutant rice lines, MR219 line 4 and line 9. The mature embryos were isolated and cultured on an MS medium with different hygromycin concentrations (0, 20, 40, 60, 80 and 100 mg L(-1)). Evidently, above 60 mg L(-1) was effective for callus formation and observed completely dead. Further there were tested for specific concentration (0-60). Although, 21.28% calli survived on the medium containing 45 mg L(-1) hygromycin, it seemed suitable for the identification of putative transformants. These findings indicated that a system for rice transformation in a relatively high frequency and the transgenes are stably expressed in the transgenic plants. Green shoots were regenerated from the explant under hygromycin stress. RT-PCR using hptII and gus sequence specific primer and Southern blot analysis were used to confirm the presence of the transgene and to determine the transformation efficiency for their stable integration in regenerated plants. This study demonstrated that the hygromycin resistance can be used as an effective marker for rice transformation.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  10. Fulltext Phenotypic detection of metallo-β-lactamase in imipenem-resistant Pseudomonas aeruginosa
    Khosravi Y, Loke MF, Chua EG, Tay ST, Vadivelu J
    ScientificWorldJournal, 2012;2012:654939.
    PMID: 22792048 DOI: 10.1100/2012/654939
    Carbapenems are the primary choice of treatment for severe Pseudomonas aeruginosa infection. However, the emergence of carbapenem resistance due to the production of metallo-β-lactamases (MBLs) is of global concern. In this study, 90 imipenem- (IPM- or IP-) resistant P. aeruginosa (IRPA) isolates, including 32 previously tested positive and genotyped for MBL genes by PCR, were subjected to double-disk synergy test (DDST), combined disk test (CDT), and imipenem/imipenem-inhibitor (IP/IPI) E-test to evaluate their MBLs detection capability. All three methods were shown to have a sensitivity of 100%. However, DDST was the most specific of the three (96.6%), followed by IP/IPI E-test interpreted based on the single criteria of IP/IPI ≥8 as positive (62.1%), and CDT was the least specific (43.1%). Based on the data from this evaluation, we propose that only IRPA with IP MIC >16 μg/mL and IP/IPI ≥8 by IP/IPI E-test should be taken as positive for MBL activity. With the new dual interpretation criteria, the MBL IP/IPI E-test was shown to achieve 100% sensitivity as well as specificity for the IRPA in this study. Therefore, the IP/IPI E-test is a viable alternative phenotypic assay to detect MBL production in IRPA in our population in circumstances where PCR detection is not a feasible option.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  11. Occurrence and contamination profiles of antibiotic resistance genes from swine manure to receiving environments in Guangdong Province southern China
    Wen X, Mi J, Wang Y, Ma B, Zou Y, Liao X, et al.
    Ecotoxicol Environ Saf, 2019 May 30;173:96-102.
    PMID: 30769208 DOI: 10.1016/j.ecoenv.2019.02.023
    Livestock farms are commonly regarded as the main sources of antibiotic resistance genes (ARGs), emerging pollutants with potential implications for human health, in the environment. This study investigated the occurrence and contamination profiles of nine ARGs of three types from swine manure to receiving environments (soil and water) in Guangdong Province, southern China. All ARGs occurred in 100% of swine manure samples. Moreover, the absolute concentration of total ARGs varied from 3.01 × 108 to 7.18 × 1014 copies/g, which was significantly higher than that in wastewater and manured soil (p  0.05). However, the number of ARGs (ermB, qnrS, acc(6')-Ib, tetM, tetO and tetQ) decreased but were not eliminated by wastewater treatment components (p 
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  12. Fulltext Next generation sequencing reveals the antibiotic resistant variants in the genome of Pseudomonas aeruginosa
    Ramanathan B, Jindal HM, Le CF, Gudimella R, Anwar A, Razali R, et al.
    PLoS One, 2017;12(8):e0182524.
    PMID: 28797043 DOI: 10.1371/journal.pone.0182524
    Rapid progress in next generation sequencing and allied computational tools have aided in identification of single nucleotide variants in genomes of several organisms. In the present study, we have investigated single nucleotide polymorphism (SNP) in ten multi-antibiotic resistant Pseudomonas aeruginosa clinical isolates. All the draft genomes were submitted to Rapid Annotations using Subsystems Technology (RAST) web server and the predicted protein sequences were used for comparison. Non-synonymous single nucleotide polymorphism (nsSNP) found in the clinical isolates compared to the reference genome (PAO1), and the comparison of nsSNPs between antibiotic resistant and susceptible clinical isolates revealed insights into the genome variation. These nsSNPs identified in the multi-drug resistant clinical isolates were found to be altering a single amino acid in several antibiotic resistant genes. We found mutations in genes encoding efflux pump systems, cell wall, DNA replication and genes involved in repair mechanism. In addition, nucleotide deletions in the genome and mutations leading to generation of stop codons were also observed in the antibiotic resistant clinical isolates. Next generation sequencing is a powerful tool to compare the whole genomes and analyse the single base pair variations found within the antibiotic resistant genes. We identified specific mutations within antibiotic resistant genes compared to the susceptible strain of the same bacterial species and these findings may provide insights to understand the role of single nucleotide variants in antibiotic resistance.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  13. Mutations in Genes Encoding 23S rRNA and FadD32 May be Associated with Linezolid Resistance in Mycobacteroides abscessus
    Ng HF, Ngeow YF
    Microb Drug Resist, 2023 Feb;29(2):41-46.
    PMID: 36802272 DOI: 10.1089/mdr.2022.0068
    Linezolid is one of the antibiotics used to treat the Mycobacteroides abscessus infection. However, linezolid-resistance mechanisms of this organism are not well understood. The objective of this study was to identify possible linezolid-resistance determinants in M. abscessus through characterization of step-wise mutants selected from a linezolid-susceptible strain, M61 (minimum inhibitory concentration [MIC]: 0.25 mg/L). Whole-genome sequencing and subsequent PCR verification of the resistant second-step mutant, A2a(1) (MIC: >256 mg/L), revealed three mutations in its genome, two of which were found in the 23S rDNA (g2244t and g2788t) and another one was found in a gene encoding the fatty-acid-CoA ligase FadD32 (c880t→H294Y). The 23S rRNA is the molecular target of linezolid and mutations in this gene are likely to contribute to resistance. Furthermore, PCR analysis revealed that the c880t mutation in the fadD32 gene first appeared in the first-step mutant, A2 (MIC: 1 mg/L). Complementation of the wild-type M61 with the pMV261 plasmid carrying the mutant fadD32 gene caused the previously sensitive M61 to develop a reduced susceptibility to linezolid (MIC: 1 mg/L). The findings of this study uncovered hitherto undescribed mechanisms of linezolid resistance in M. abscessus that may be useful for the development of novel anti-infective agents against this multidrug-resistant pathogen.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  14. Fulltext Molecular detection and antimicrobial resistance profiles of Extended-Spectrum Beta-Lactamase (ESBL) producing Escherichia coli in broiler chicken farms in Malaysia
    Lemlem M, Aklilu E, Mohammed M, Kamaruzzaman F, Zakaria Z, Harun A, et al.
    PLoS One, 2023;18(5):e0285743.
    PMID: 37205716 DOI: 10.1371/journal.pone.0285743
    Antimicrobial resistance is one of the major public health threats globally. This challenge has been aggravated with the overuse and misuse of antibiotics in food animals and humans. The present study aimed to investigate the prevalence of Extended-Spectrum β-lactamase (ESBL) genes in Escherichia coli (E. coli) isolated from broiler chickens in Kelantan, Malaysia. A total of 320 cloacal swabs were collected from farms in different districts of Kelantan and were analyzed using routine bacteriology, antimicrobial susceptibility test, and molecular techniques for further identification and characterization of ESBL encoding genes. Based on PCR detection for the E. coli species-specific Pho gene, 30.3% (97/320) of isolates were confirmed as E. coli, and 84.5% (82/97) of the isolates were positive for at least one ESBL gene. Majority of the isolates, 62.9% (61/97) were harboring blaCTX-M followed by 45.4% (44/97) of blaTEM genes, while 16.5% (16/97) of the isolates were positive for both mcr-1 and ESBL genes. Overall, 93.8% (90/97) of the E. coli were resistant to three or more antimicrobials; indicating that the isolates were multi-drug resistance. 90.7% of multiple antibiotic resistance (MAR) index value greater than 0.2, would also suggest the isolates were from high-risk sources of contamination. The MLST result shows that the isolates are widely diverse. Our findings provide insight into the alarmingly high distribution of antimicrobial resistant bacteria, mainly ESBL producing E. coli in apparently healthy chickens indicating the role of food animals in the emergence and spread of antimicrobial resistance, and the potential public health threats it may pose.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  15. Molecular characterization showed limited genetic diversity among Salmonella Enteritidis isolated from humans and animals in Malaysia
    Ngoi ST, Thong KL
    Diagn Microbiol Infect Dis, 2013 Dec;77(4):304-11.
    PMID: 24139970 DOI: 10.1016/j.diagmicrobio.2013.09.004
    Salmonella enterica serovar Enteritidis (S. Enteritidis) is the most common causative agent of non-typhoidal salmonellosis in Malaysia. We aimed to characterize S. Enteritidis isolated from humans and animals by analyzing their antimicrobial resistance profiles and genotypes. A total of 111 strains were characterized using multiple-locus variable-number tandem repeat analysis, pulsed-field gel electrophoresis, and antimicrobial susceptibility testing. Both typing methods revealed that genetically similar S. Enteritidis strains had persisted among human and animal populations within the period of study (2003-2008). Only 39% of the strains were multi-drug resistant (i.e., resistant to 3 or more classes of antimicrobial agents), with a majority (73%) of these in low-risk phase (multiple antibiotic resistant index <0.20). Limited genetic diversity among clinical and zoonotic S. Enteritidis suggested that animals are possible sources of human salmonellosis. The degree of multi-drug resistance among the strains was generally low during the study period.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  16. Molecular characterization of genes encoding the quinolone resistance determining regions of Malaysian Streptococcus pneumoniae strains
    Kumari N, Subramaniam G, Navaratnam P, Sekaran SD
    Indian J Med Microbiol, 2008 5 1;26(2):148-50.
    PMID: 18445951
    Genes encoding the quinolones resistance determining regions (QRDRs) in Streptococcus pneumoniae were detected by PCR and the sequence analysis was carried out to identify point mutations within these regions. The study was carried out to observe mutation patterns among S. pneumoniae strains in Malaysia. Antimicrobial susceptibility testing of 100 isolates was determined against various antibiotics, out of which 56 strains were categorised to have reduced susceptibility to ciprofloxacin (>or=2 microg/mL). These strains were subjected to PCR amplification for presence of the gyrA, parC , gyrB and parE genes. Eight representative strains with various susceptibilities to fluoroquinolones were sequenced. Two out of the eight isolates that were sequenced were shown to have a point mutation in the gyrA gene at position Ser81. The detection of mutation at codon Ser81 of the gyrA gene suggested the potential of developing fluoroquinolone resistance among S. pneumoniae isolates in Malaysia. However, further experimental work is required to confirm the involvement of this mutation in the development of fluoroquinolone resistance in Malaysia.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  17. Fulltext Molecular characterization of extended-spectrum β-lactamase-producing Klebsiella pneumoniae from a Malaysian hospital
    Mobasseri G, Thong KL, Rajasekaram G, Teh CSJ
    Braz J Microbiol, 2020 Mar;51(1):189-195.
    PMID: 31838661 DOI: 10.1007/s42770-019-00208-w
    Multidrug-resistant (MDR) and extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae associated with nosocomial infections have caused serious problems in antibiotic management with limited therapeutic choices. This study aimed to determine the genotypic and phenotypic characteristics of K. pneumoniae strains isolated from a tertiary hospital in Malaysia. Ninety-seven clinical K. pneumoniae strains were analyzed for antimicrobial susceptibility, all of which were sensitive to amikacin and colistin (except one strain), while 31.9 % and 27.8 % were MDR and ESBL producers, respectively. PCR and DNA sequencing of the amplicons indicated that the majority of MDR strains (26/27) were positive for blaTEM, followed by blaSHV (24/27), blaCTX-M-1 group (23/27), blaCTX-M-9 group (2/27), and mcr-1 (1/27). Thirty-seven strains were hypervirulent and PCR detection of virulence genes showed 38.1 %, 22.7 %, and 16.5 % of the strains were positive for K1, wabG, and uge genes, respectively. Genotyping by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) showed that these strains were genetically diverse and heterogeneous. Sequence types, ST23, ST22, and ST412 were the predominant genotypes. This is the first report of colistin-resistant K. pneumoniae among clinical strains associated with mcr-1 plasmid in Malaysia. The findings in this study have contributed to the effort in combating the increase in antimicrobial resistance by providing better understanding of genotypic characteristics and resistance mechanisms of the organisms.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  18. Molecular analysis of ciprofloxacin resistance among non-typhoidal Salmonella with reduced susceptibility to ciprofloxacin isolated from patients at a tertiary care hospital in Kuala Lumpur, Malaysia
    Karunakaran R, Tay ST, Rahim FF, Lim BB, Puthucheary SD
    Jpn J Infect Dis, 2014;67(3):157-62.
    PMID: 24858603
    We investigated the prevalence of non-typhoidal Salmonella (NTS) with "reduced susceptibility to ciprofloxacin" (RS-Cip) (minimum inhibitory concentration [MIC], 0.12-1.0 μg/mL) as well as their resistance genes in 75 NTS isolates (53 from stool, 21 from blood, and 1 from urine) from patients at a tertiary care Malaysian hospital between January and December 2009. RS-Cip was detected in 24/75 (32.0%) isolates. Using the ciprofloxacin MIC interpretive criteria for Salmonella in the Clinical and Laboratory Standards Institute 2013 guidelines, 51/75 (68.0%) isolates were found to be sensitive, 22/75 (29.3%) were intermediate, and 2/75 (2.7%) were resistant to ciprofloxacin. The 24 isolates that were intermediate or resistant to ciprofloxacin were the same isolates categorized as having RS-Cip. Among the 23 tested isolates with RS-Cip, the qnrS gene was detected in 17/23 (73.9%) and single gyrA mutations were detected in 6/23 (26.1%) (Asp87Tyr [n = 3], Asp87Asn [n = 2], and Ser83Phe [n = 1]). A parC (Thr57Ser) mutation was detected in 13/23 (56.5%) isolates, coexisting with either a qnrS gene or a gyrA mutation. The high incidence of the qnrS gene among isolates with RS-Cip needs to be monitored because qnr genes can spread via plasmids and aid in the emergence of increased resistance levels.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  19. Modifications in the pmrB gene are the primary mechanism for the development of chromosomally encoded resistance to polymyxins in uropathogenic Escherichia coli
    Phan MD, Nhu NTK, Achard MES, Forde BM, Hong KW, Chong TM, et al.
    J Antimicrob Chemother, 2017 10 01;72(10):2729-2736.
    PMID: 29091192 DOI: 10.1093/jac/dkx204
    Objectives: Polymyxins remain one of the last-resort drugs to treat infections caused by MDR Gram-negative pathogens. Here, we determined the mechanisms by which chromosomally encoded resistance to colistin and polymyxin B can arise in the MDR uropathogenic Escherichia coli ST131 reference strain EC958.

    Methods: Two complementary approaches, saturated transposon mutagenesis and spontaneous mutation induction with high concentrations of colistin and polymyxin B, were employed to select for mutations associated with resistance to polymyxins. Mutants were identified using transposon-directed insertion-site sequencing or Illumina WGS. A resistance phenotype was confirmed by MIC and further investigated using RT-PCR. Competitive growth assays were used to measure fitness cost.

    Results: A transposon insertion at nucleotide 41 of the pmrB gene (EC958pmrB41-Tn5) enhanced its transcript level, resulting in a 64- and 32-fold increased MIC of colistin and polymyxin B, respectively. Three spontaneous mutations, also located within the pmrB gene, conferred resistance to both colistin and polymyxin B with a corresponding increase in transcription of the pmrCAB genes. All three mutations incurred a fitness cost in the absence of colistin and polymyxin B.

    Conclusions: This study identified the pmrB gene as the main chromosomal target for induction of colistin and polymyxin B resistance in E. coli.

    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  20. Fulltext MgrB Mutations and Altered Cell Permeability in Colistin Resistance in Klebsiella pneumoniae
    Yap PS, Cheng WH, Chang SK, Lim SE, Lai KS
    Cells, 2022 Sep 26;11(19).
    PMID: 36230959 DOI: 10.3390/cells11192995
    There has been a resurgence in the clinical use of polymyxin antibiotics such as colistin due to the limited treatment options for infections caused by carbapenem-resistant Enterobacterales (CRE). However, this last-resort antibiotic is currently confronted with challenges which include the emergence of chromosomal and plasmid-borne colistin resistance. Colistin resistance in Klebsiella pneumoniae is commonly caused by the mutations in the chromosomal gene mgrB. MgrB spans the inner membrane and negatively regulates PhoP phosphorylation, which is essential for bacterial outer membrane lipid biosynthesis. The present review intends to draw attention to the role of mgrB chromosomal mutations in membrane permeability in K. pneumoniae that confer colistin resistance. With growing concern regarding the global emergence of colistin resistance, deciphering physical changes of the resistant membrane mediated by mgrB inactivation may provide new insights for the discovery of novel antimicrobials that are highly effective at membrane penetration, in addition to finding out how this can help in alleviating the resistance situation.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
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