scholarly journals Acquisition and Spread of Antimicrobial Resistance: A tet(X) Case Study

2021 ◽  
Vol 22 (8) ◽  
pp. 3905
Author(s):  
Rustam Aminov

Understanding the mechanisms leading to the rise and dissemination of antimicrobial resistance (AMR) is crucially important for the preservation of power of antimicrobials and controlling infectious diseases. Measures to monitor and detect AMR, however, have been significantly delayed and introduced much later after the beginning of industrial production and consumption of antimicrobials. However, monitoring and detection of AMR is largely focused on bacterial pathogens, thus missing multiple key events which take place before the emergence and spread of AMR among the pathogens. In this regard, careful analysis of AMR development towards recently introduced antimicrobials may serve as a valuable example for the better understanding of mechanisms driving AMR evolution. Here, the example of evolution of tet(X), which confers resistance to the next-generation tetracyclines, is summarised and discussed. Initial mechanisms of resistance to these antimicrobials among pathogens were mostly via chromosomal mutations leading to the overexpression of efflux pumps. High-level resistance was achieved only after the acquisition of flavin-dependent monooxygenase-encoding genes from the environmental microbiota. These genes confer resistance to all tetracyclines, including the next-generation tetracyclines, and thus were termed tet(X). ISCR2 and IS26, as well as a variety of conjugative and mobilizable plasmids of different incompatibility groups, played an essential role in the acquisition of tet(X) genes from natural reservoirs and in further dissemination among bacterial commensals and pathogens. This process, which took place within the last decade, demonstrates how rapidly AMR evolution may progress, taking away some drugs of last resort from our arsenal.

1998 ◽  
Vol 42 (12) ◽  
pp. 3276-3278 ◽  
Author(s):  
Amera Gibreel ◽  
Eva Sjögren ◽  
Bertil Kaijser ◽  
Bengt Wretlind ◽  
Ola Sköld

ABSTRACT Quinolone resistance in clinical isolates of Campylobacter jejuni in Sweden increased more than 20-fold at the beginning of the 1990s. Resistance to 125 μg of ciprofloxacin per ml in clinical isolates was associated with chromosomal mutations in C. jejuni leading to a Thr-86-Ile substitution in thegyrA product and a Arg-139-Gln substitution in theparC product.


Author(s):  
P Salmerón ◽  
A Moreno-Mingorance ◽  
J Trejo ◽  
R Amado ◽  
B Viñado ◽  
...  

Abstract Background Neisseria gonorrhoeae (NG) isolates with high-level azithromycin resistance (HL-AziR) have emerged worldwide in recent decades, threatening the sustainability of current dual-antimicrobial therapy. Objectives This study aimed to characterize the first 16 NG isolates with HL-AziR in Barcelona between 2016 and 2018. Methods WGS was used to identify the mechanisms of antimicrobial resistance, to establish the MLST ST, NG multiantigen sequence typing (NG-MAST) ST and NG sequence typing for antimicrobial resistance (NG-STAR) ST and to identify the clonal relatedness of the isolates with other closely related NG previously described in other countries based on a whole-genome SNP analysis approach. The sociodemographic characteristics of the patients included in the study were collected by comprehensive review of their medical records. Results Twelve out of 16 HL-AziR isolates belonged to the MLST ST7823/NG-MAST ST5309 genotype and 4 to MLST ST9363/NG-MAST ST3935. All presented the A2059G mutation in all four alleles of the 23S rRNA gene. MLST ST7823/NG-MAST ST5309 isolates were only identified in men who have sex with women and MLST ST9363/NG-MAST ST3935 were found in MSM. Phylogenomic analysis revealed the presence of three transmission clusters of three different NG strains independently associated with sexual behaviour. Conclusions Our findings support the first appearance of three mild outbreaks of NG with HL-AziR in Spain. These results highlight the continuous capacity of NG to develop antimicrobial resistance and spread among sexual networks. The enhanced resolution of WGS provides valuable information for outbreak investigation, complementing the implementation of public health measures focused on the prevention and dissemination of MDR NG.


2019 ◽  
Vol 7 (11) ◽  
pp. 579 ◽  
Author(s):  
Jae-Ho Guk ◽  
Junhyung Kim ◽  
Hyokeun Song ◽  
Jinshil Kim ◽  
Jae-Uk An ◽  
...  

Campylobacter, a common foodborne human pathogen, is considered sensitive to oxygen. Recently, aerotolerant (AT) Campylobacter jejuni with the ability to survive under aerobic stress has been reported. Here, we investigated the prevalence of hyper-aerotolerant (HAT) Campylobacter coli from duck sources (118 carcasses and meat) and its characteristics to assess potential impacts on public health. Half of 56 C. coli isolates were HAT and most harbored various virulence genes including flaA, cadF, cdtA, ceuB, and wlaN. Moreover, 98.2% of C. coli isolates showed resistance to quinolones, including ciprofloxacin (CIP), and nine (16.1%) showed high-level resistance to ciprofloxacin (Minimum Inhibitory Concentration, MIC ≥ 32 μg/mL) and most of these were HAT. Based on genetic relatedness between C. coli from duck sources and those from human sources (PubMLST and NCBI), HAT isolates sharing the same MLST sequence types were significantly more prevalent than those not sharing the same sequence types as those from human sources. Therefore, HAT C. coli is prevalent in duck sources, and is most likely transmitted to humans through the food chain given its aerotolerance. This being so, it might pose a threat to public health given its virulence and antimicrobial resistance (AMR). This study will assist in improving control strategies to reduce farm-to-table HAT C. coli transmission to humans.


2010 ◽  
Vol 54 (6) ◽  
pp. 2728-2731 ◽  
Author(s):  
A. Morvan ◽  
C. Moubareck ◽  
A. Leclercq ◽  
M. Hervé-Bazin ◽  
S. Bremont ◽  
...  

ABSTRACT Susceptibility to antibiotics of 4,816 clinical L. monocytogenes strains isolated since 1926 was studied, and the temporal evolution of susceptibility to antibiotics was analyzed through several decades. The mechanisms of resistance in each resistant strain were studied. The prevalence of resistant strains was estimated at 1.27% among isolates from humans. Resistance to tetracyclines+ and fluoroquinolones was more common and has recently emerged. Although acquired resistance in clinical L. monocytogenes did not implicate clinically relevant antibiotics, the possibility of resistance gene transfers, the description of the first clinical isolate with high-level resistance to trimethoprim, and the recent increase in penicillin MICs up to 2 μg/ml reinforce the need for microbiological surveillance.


2011 ◽  
Vol 74 (10) ◽  
pp. 1639-1648 ◽  
Author(s):  
CINDY-LOVE TREMBLAY ◽  
ANN LETELLIER ◽  
SYLVAIN QUESSY ◽  
MARTINE BOULIANNE ◽  
DANIELLE DAIGNAULT ◽  
...  

This study was conducted to characterize the antimicrobial resistance determinants and investigate plasmid colocalization of tetracycline and macrolide genes in Enterococcus faecalis and Enterococcus faecium from broiler chicken and turkey flocks in Canada. A total of 387 E. faecalis and E. faecium isolates were recovered from poultry cecal contents from five processing plants. The percentages of resistant E. faecalis and E. faecium isolates, respectively, were 88.1 and 94% to bacitracin, 0 and 0.9% to chloramphenicol, 0.7 and 14.5% to ciprofloxacin, 72.6 and 80.3% to erythromycin, 3.7 and 41% to flavomycin, 9.6 and 4.3% (high-level resistance) to gentamicin, 25.2 and 17.1% (high-level resistance) to kanamycin, 100 and 94% to lincomycin, 0 and 0% to linezolid, 2.6 and 20.5% to nitrofurantoin, 3 and 27.4% to penicillin, 98.5 and 89.7% to quinupristin-dalfopristin, 7 and 12.8% to salinomycin, 46.7 and 38.5% (high-level resistance) to streptomycin, 95.6 and 89.7% to tetracycline, 73 and 75.2% to tylosin, and 0 and 0% to vancomycin. One predominant multidrug-resistant phenotypic pattern was identified in both E. faecalis and E. faecium (bacitracin, erythromycin, lincomycin, quinupristin-dalfopristin, tetracycline, and tylosin). These isolates were further examined by PCR and sequencing for the genes encoding their antimicrobial resistance. Various combinations of vatD, vatE, bcrR, bcrA, bcrB, bcrD, ermB, msrC, linB, tetM, and tetO genes were detected, and ermB, tetM, and bcrB were the most common antimicrobial resistance genes identified. For the first time, plasmid extraction and hybridization revealed colocalization of tetO and ermB genes on a ca. 11-kb plasmid in E. faecalis isolates, and filter mating experiments demonstrated its transferability. Results indicate that the intestinal enterococci of healthy poultry, which can contaminate poultry meat at slaughter, could be a reservoir for quinupristin-dalfopristin, bacitracin, tetracycline, and macrolide resistance genes.


2012 ◽  
Vol 64 (4) ◽  
pp. 1301-1309 ◽  
Author(s):  
Valentina Nikolic ◽  
D. Salemovic ◽  
Dj. Jevtovic ◽  
I. Pesic-Pavlovic ◽  
S. Zerjav ◽  
...  

Transmitted drug resistance (TDR) is one of the consequences of the high variability of HIV-1. The widespread use of antiretroviral therapy for the treatment of HIV-1 infection results in a large circulating pool of resistant virus variants. It is known that TDR mutations can persist for extended periods and may pose an important problem to the overall success of antiretroviral therapy. Factors that determine the duration of continuous persistence of resistance-associated mutations are the number and type of these mutations and their impact on viral fitness. Here we describe the follow-up of a case study of prolonged persistence of resistance-associated mutations, namely RT mutations Q151M, K65KR and Y181C conferring an intermediate-to-high level resistance to multiple NRTIs and NNRTIs that lasted for seven years. The infection was caused by subtype G virus.


Antibiotics ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 58 ◽  
Author(s):  
Ranmini Kularatne ◽  
Venessa Maseko ◽  
Lindy Gumede ◽  
Tendesayi Kufa

Background: In South Africa, sexually transmitted infections (STIs) are managed through a syndromic approach at primary healthcare centres (PHCs). Neisseria gonorrhoeae is the predominant cause of male urethritis syndrome. We describe antimicrobial resistance patterns and trends in Neisseria gonorrhoeae during a ten-year surveillance period at a large PHC in Johannesburg. Methods: Neisseria gonorrhoeae was cultured from genital discharge swab specimens obtained from consenting adult patients presenting at the Alexandra Health Centre in Johannesburg between 2008 and 2017. Isolates were tested for antimicrobial susceptibility by Etest™ (cefixime, ceftriaxone, ciprofloxacin) or agar dilution (penicillin, tetracycline, azithromycin). Results: During the period of surveillance, high-level resistance prevalence increased from 30% to 51% for penicillin (p-value for trend < 0.001), 75% to 83% for tetracycline (p-value for trend = 0.008), and 25% to 69% for ciprofloxacin (p-value for trend < 0.001). Analysis did not reveal high-level resistance to spectinomycin or a minimum inhibitory concentration (MIC) creep for extended-spectrum cephalosporins, and the prevalence of intermediate-resistance to azithromycin was less than 5%. Conclusions: High prevalence resistance to penicillin, tetracycline, and ciprofloxacin in N. gonorrhoeae obviates their use in future national treatment algorithms for genital discharge. It is essential to continue monitoring for emerging resistance to currently recommended antimicrobial therapy in this rapidly evolving pathogen.


2018 ◽  
Vol 63 (2) ◽  
pp. e00712-18 ◽  
Author(s):  
Miki Matsuo ◽  
Norio Yamamoto ◽  
Tomomi Hishinuma ◽  
Keiichi Hiramatsu

ABSTRACTβ-Lactam resistance levels vary among methicillin-resistantStaphylococcus aureus(MRSA) clinical isolates, mediated by chromosomal mutations and exogenous resistance genemecA. However, MRSA resistance mechanisms are incompletely understood. A P440L mutation in the RNA polymerase β′ subunit (RpoC) in slow-vancomycin-intermediateS. aureus(sVISA) strain V6-5 is associated with conversion of heterogeneous VISA (hVISA) to sVISA. In this study, we found a V6-5-derivative strain (L4) with significantly decreased MICs to oxacillin (OX) and vancomycin. Whole-genome sequencing revealed that L4 has nonsense mutations in two genes,relQ, encoding (p)ppGpp synthetase, an alarmone of the stringent response, and a gene of unknown function.relQdeletion in the hVISA strain Mu3 did not affect OX MIC. However, introducing nonsense mutation of the unknown gene into Mu3 decreased OX MIC, whereas wild-type gene recovered high-level resistance. Thus, mutation of this unknown gene (ehoM) decreased β-lactam resistance in Mu3 and L4. Presence ofrelQin a multicopy plasmid restored high-level resistance in strain L4 but not in theehoMmutant Mu3 strain, indicating a genetic interaction betweenehoMandrelQdepending on the L4 genetic background. While mupirocin (a stringent response inducer) can increase the β-lactam resistance of MRSA, mupirocin supplementation in anehoMdeletion mutant of N315 did not elevate resistance.ehoMexpression in N315 was induced by mupirocin, and the relative amount ofehoMtranscript in Mu3 was higher than in N315 induced by the stringent response. Our findings indicate thatehoMplays an essential role in high-level β-lactam resistance in MRSA via the stringent response.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Manal Diab ◽  
Dalia Salem ◽  
Ahmed El-Shenawy ◽  
Amira El-Far ◽  
Aya Abdelghany ◽  
...  

Abstract Background Enterococci are intrinsically resistant to clinically achievable concentrations of aminoglycosides. However, high-level resistance to aminoglycosides (HLAR) is primarily due to the acquisition of genes encoding aminoglycoside-modifying enzymes (AMEs). Aminoglycosides along with cell wall inhibitors are given clinically for treating enterococcal infections. The current study was conducted to investigate the rate of HLAR and to determine aminoglycoside resistance encoding genes profile in enterococcal isolates from different clinical specimens. Results From 120 Enterococcus species, 50 (41.7%) enterococcal isolates were proven to have HLAR, 78% (39/50) have high-level gentamicin resistance (HLGR), and 74% (37/50) were high-level streptomycin-resistant (HLSR). HLGR isolates carried aminoglycoside modifying gene aac (6′)-Ie-aph (2′)-Ia in 26/39 (66.7%) of isolates, whereas 32/37 (86.5%) of HLSR carried aph (3′)-IIIa gene and were observed in E. faecalis, E. faecium, E. gallinarum, and E. casseliflavus. The aph (2′)-Ib, aph (2′)-Ic, and aph (2′)-Id that encode HLGR could not be detected. Conclusions The high detection rate of HLAR among the studied Enterococcus species and the coexistence of HLGR and HLSR strains provide crucial insights to the necessity of routine testing for HLAR in the microbiology lab. The main AME genes among HLGR and HLSR enterococci were aac (6′)-Ie-aph (2″)-Ia and aph (3′)-IIIa, respectively.


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