spp. is an important zoonotic pathogen related to foodborne diseases. Despite that quinolones/fluoroquinolones are considered a relevant therapeutic strategy against resistant isolates, the increase ...in antimicrobial resistance is an additional difficulty in controlling bacterial infections caused by
spp. Thus, the acquisition of resistance to quinolones in
spp. is worrisome to the scientific community along with the possibility of transmission of resistance through plasmids. This study investigated the prevalence of plasmid-mediated quinolone resistance (PMQR) in
spp. and its association with fluoroquinolone susceptibility in Brazil. We evaluated 129 isolates, 39 originated from food of animal sources, and 14 from environmental samples and including 9 from animals and 67 from humans, which were referred to the National Reference Laboratory of Enteric Diseases (NRLEB/IOC/RJ) between 2009 and 2013. These samples showed a profile of resistance for the tested quinolones/fluoroquinolones. A total of 33 serotypes were identified;
. Typhimurium (63) was the most prevalent followed by
. Enteritidis (25). The disk diffusion test showed 48.8% resistance to enrofloxacin, 42.6% to ciprofloxacin, 39.53% to ofloxacin, and 30.2% to levofloxacin. According to the broth microdilution test, the resistance percentages were: 96.1% to nalidixic acid, 64.3% to enrofloxacin, 56.6% to ciprofloxacin, 34.1% to ofloxacin, and 30.2% to levofloxacin.
genes were found in 15 isolates (8
S, 6
B, and 1
D), and the aac(6')-Ib gene in 23. The integron gene was detected in 67 isolates with the variable region between ±600 and 1000 bp. The increased detection of PMQR in
spp. is a serious problem in Public Health and must constantly be monitored. Pulsed-field gel electrophoresis was performed to evaluated clonal profile among the most prevalent serovars resistant to different classes of quinolones. A total of 33 pulsotypes of
. Typhimurium were identified with a low percentage of genetic similarity (≤65%). This result demonstrates the presence of high diversity in the resistant clones evaluated in this study.
Abstract
Background
Quinolones are broad-spectrum antibiotics, which are used for the treatment of different infectious diseases associated with Enterobacteriaceae. During recent decades, the wide ...use as well as overuse of quinolones against diverse infections has led to the emergence of quinolone-resistant bacterial strains. Herein, we present the development of quinolone antibiotics, their function and also the different quinolone resistance mechanisms in Enterobacteriaceae by reviewing recent literature.
Methods
All data were extracted from Google Scholar search engine and PubMed site, using keywords; quinolone resistance, Enterobacteriaceae, plasmid-mediated quinolone resistance, etc.
Results and conclusion
The acquisition of resistance to quinolones is a complex and multifactorial process. The main resistance mechanisms consist of one or a combination of target-site gene mutations altering the drug-binding affinity of target enzymes. Other mechanisms of quinolone resistance are overexpression of AcrAB-tolC multidrug-resistant efflux pumps and downexpression of porins as well as plasmid-encoded resistance proteins including Qnr protection proteins, aminoglycoside acetyltransferase (AAC(6′)-Ib-cr) and plasmid-encoded active efflux pumps such as OqxAB and QepA. The elucidation of resistance mechanisms will help researchers to explore new drugs against the resistant strains.
Fluoroquinolone-resistant
is considered a serious public health problem and has been put on the WHO global priority list of antibiotic-resistant bacteria. This study was aimed to investigate the ...fluoroquinolone resistance in
and its relevant genetic mechanisms.
isolates that were isolated from diarrheal patient's feces in Ningbo China from 2011 to 2018 were tested for susceptibility to ampicillin, gentamicin, tetracycline, nalidixic acid, ciprofloxacin, and cefotaxime. Genes related to quinolone resistance were amplified by PCR.
A total of 118
isolates were collected, including 76
isolates, 40
isolates, and 2
isolates. Ciprofloxacin susceptibility test identified 10 (9%) susceptible, 65 (55%) intermediate, and 43 (36%) resistant isolates. Of 76
isolates, 37 were ciprofloxacin resistant, a prevalence significantly higher than 6 of 40
isolates (
=0.01). The isolates collected during 2014-2018 displayed a significant increase in the prevalence of ciprofloxacin resistance (
=0.05) than those collected during 2011-2013. All the ciprofloxacin-intermediate and resistant isolates had mutations of
(S83L) and
(S80I), whereas only the ciprofloxacin-resistant isolates had
(D87N) mutation and
gene. Additionally, 30% of the ciprofloxacin-resistant isolates were positive for
gene.
This study shows the currently increasing prevalence of ciprofloxacin resistance. The reduced fluoroquinolone susceptibility is highly associated with
(S83L) and
(S80I) mutations, while the fluoroquinolone resistance is highly associated with
(D87N) mutation,
gene and perhaps
gene.
The environment has been identified as an origin, reservoir, and transmission route of antibiotic resistance genes (ARGs). Among diverse environments, freshwater environments have been recognized as ...pivotal in the transmission of ARGs between opportunistic pathogens and autochthonous bacteria such as Aeromonas spp. In this study, five environmental strains of Aeromonas spp. exhibiting multidrug resistance (MDR) were selected for whole-genome sequencing to ascertain their taxonomic assignment at the species-level and to delineate their ARG repertoires. Analyses of their genomes revealed the presence of one protein almost identical to AhQnr (A. hydrophila Qnr protein) and four novel proteins similar to AhQnr. To scrutinize the classification and taxonomic distribution of these proteins, all Aeromonas genomes deposited in the NCBI RefSeq genome database (1,222 genomes) were investigated. This revealed that these Aeromonas Qnr (AQnr) proteins are conserved intrinsic resistance determinants of the genus, exhibiting speciesspecific diversity. Additionally, structure prediction and analysis of contribution to quinolone resistance by AQnr proteins of the isolates, confirmed their functionality as quinolone resistance determinants. Given the origin of mobile qnr genes from aquatic bacteria and the crucial role of Aeromonas spp. in ARG dissemination in aquatic environments, a thorough understanding and strict surveillance of AQnr families prior to the clinical emergence are imperative. In this study, using comparative genome analyses and functional characterization of AQnr proteins in the genus Aeromonas, novel Aeromonas ARGs requiring surveillance has suggested.
This study aimed to investigate the antimicrobial resistance profile to quinolones, the presence of quinolone‐resistant determinants and the plasmid replicon typing in environmental Achromobacter sp. ...isolated from Brazil. Soil and water samples were used for bacterial isolation. The antimicrobial susceptibility testing was performed by minimum inhibitory concentration method. The detection of mutations in the quinolone resistance‐determining regions (QRDR) genes, the presence of plasmid‐mediated quinolone resistance (PMQR) genes, and plasmid replicons were performed by PCR. A total of 16 isolates was obtained from different cultures, cities, and states of Brazil. All isolates were non‐susceptible to ciprofloxacin, norfloxacin, and levofloxacin. Some mutations in QRDR genes were found, including Gln‐83‐Leu and Asp‐87‐Asn in the gyrA and Gln‐80‐Ile and Asp‐84‐Ala in the parC. Different PMQR genes were detected, such as qnrA, qnrB, qnrS, oqxA, and oqxB. Three different plasmid families were detected, being most presented the ColE‐like, followed by IncFIB and IncA/C. The presence of different PMQR genes and plasmids in the isolates of the present study shows that environmental bacteria can act as reservoir of important genes of resistance to fluoroquinolones, which is of great concern, due to the potential of horizontal dissemination of these genes. Besides that, there are no studies reporting these results in Achromobacter sp. isolates.
For 29 parent strains, recognized by pulsed-field gel electrophoresis, the MICs multiplied significantly in the ciprofloxacin group than levofloxacin group, following the first and third induction ...cycle. Ser83Arg in GyrA was the most common site of mutations. No mutation in ParC nor ParE was identified in the selected mutants.
Escherichia coli is the leading causative agent of bovine mastitis worldwide. Quinolone-resistant E. coli is becoming a potential threat to veterinary and public health. The aim of this study was to ...investigate the characteristics of quinolone-resistant E. coli isolated from bovine mastitis cases in China. Antimicrobial susceptibility of the isolates against 15 antimicrobial agents was determined by disc diffusion method. Phylogenetic grouping was detected by PCR. Extended-spectrum β-lactamase-producing isolates were determined by double-disc synergy test. In addition, the plasmid-mediated quinolone resistance (PMQR) and β-lactamase-encoding genes, as well as mutations of quinolone resistance-determining regions in GyrA, GyrB, ParC, and ParE, were measured by PCR and DNA sequencing. Overall, 75 (22.9%) out of 328 E. coli isolates were confirmed as ciprofloxacin-resistant from 2,954 mastitic milk samples. Phylogenetic group analysis showed that the majority of these strains belonged to phylogenetic group A (57.3%) and group B1 (24.0%). All the resistant isolates were identified as multidrug resistant, showing high resistance to cephalosporins and non-β-lactams. Forty-nine (65.3%) of the quinolone-resistant isolates were positive for PMQR genes; aac-(6')-Ib-cr was the most common PMQR determinant detected in 33 (44.0%) isolates. Eighteen (24.0%), 4 (5.3%), 3 (4.0%), and 1 (1.3%) of the quinolone-resistant isolates were harboring oqxA/B, qepA4, qnrS, and qnrB2, respectively. Additionally, 55 (73.3%) of the quinolone-resistant E. coli isolates were found to be extended-spectrum β-lactamase producers. The preponderant β-lactamase-encoding gene, blaTEM, was detected in 44 (58.7%) isolates; blaCTX-M, blaCMY, and blaSHV were found in 35 (46.7%), 22 (29.3%), and 2 (2.7%) isolates, respectively. Moreover, the most frequently identified substitutions were S83L/D87N or S83L in GyrA, detected in all of the quinolone-resistant isolates. Meanwhile, 74 (98.7%), 33 (44.0%), and 6 (8.0%) of the isolates were carrying substitutions S80I in ParC, S458A in ParE, and S492N in GyrB, respectively. All 58 (77.3%) isolates with a high level of ciprofloxacin resistance (>32 µg/mL) carried single or double mutations in GyrA combined with single mutation in ParC. To the best of our knowledge, this is the first report on the high occurrence of PMQR determinants and quinolone-determining resistant regions mutations in quinolone-resistant E. coli isolated from bovine mastitis in China.
Background:
This study analyzed the antimicrobial resistance phenotypes and mechanisms of quinolone, cephalosporins, and colistin resistance in nontyphoidal
Salmonella
from patients with diarrhea in ...Jiangsu, China.
Methods:
A total of 741 nontyphoidal
Salmonella
isolates were collected from hospitals in major cities of Jiangsu Province, China between 2016 and 2017. Their susceptibility to commonly used antibiotics was evaluated by broth micro-dilution and sequencing analysis of resistance genes screened by a PCR method. For
mcr-1
positive isolates, genetic relationship study was carried out by pulsed-field gel electrophoresis and multiloci sequence typing analysis. The transferability of these plasmids was measured with conjugation experiments and the genetic locations of
mcr-1
were analyzed by pulsed-field gel electrophoresis profiles of S1-digested genomic DNA and subsequent Southern blot hybridization.
Results:
Among 741 nontyphoidal
Salmonella
isolates, the most common serotypes identified were
S.
Typhimurium (
n
=257, 34.7%) and
S.
Enteritidis (
n
=127, 17.1%), and the isolates showed 21.7, 20.6, and 5.0% resistance to cephalosporins, ciprofloxacin, and colistin, respectively. Among the 335 nalidixic acid-resistant
Salmonella
, 213 (63.6%) and 45 (13.4%) had at least one mutation in
gyrA
and
parC
. Among the plasmid-borne resistance,
qnrS1
(85; 41.9%) and
aac(6')-Ib-cr4
(75; 36.9%) were the most common quinolone resistance (PMQR) genes, while
bla
CTX-M-14
(
n
=35) and
bla
CTX-M-55
(
n
=46) were found to be dominant extended-spectrum beta-lactamase (ESBL) genes in nontyphoidal
Salmonella
. In addition, eight
mcr-1
-harboring strains were detected since 2016 and they were predominate in children under the age of 7years. Conjugation assays showed the donor
Salmonella
strain has functional and transferable colistin resistance and Southern blot hybridization revealed that
mcr-1
was located in a high molecular weight plasmid.
Conclusion:
In nontyphoidal
Salmonella
, there is a rapidly increasing trend of colistin resistance and this is the first report of patients harboring
mcr-1
-positive
Salmonella
with a new ST type ST155 and new serotype
S.
Sinstorf. These findings demonstrate the necessity for cautious use and the continuous monitoring of colistin in clinical applications.
Bedaquiline resistance is increasingly observed in the treatment of rifampicin-resistant tuberculosis (TB), yet standardized regimens for managing bedaquiline-resistant TB are lacking. Studies ...indicate a high proportion of bedaquiline-resistant cases have previously been treated for TB, and often involve strains resistant to quinolones. Regular monitoring of the culture status in patients receiving bedaquiline resistance treatment is advised. Methods such as experimental evolution, protein modeling, genome sequencing, and phenotypic analysis have been instrumental in identifying the mechanisms of bedaquiline resistance. Specifically, variants in the Rv0678 transcriptional repressor of the MmpS5-MmpL5 efflux system are linked to this type of resistance. Bayesian probability estimates show promise in determining the genotypic–phenotypic association for bedaquiline resistance, suggesting potential utility in clinical practice. Future research should explore the practical application of Bayesian probabilities in managing bedaquiline resistance. Sequencing-based technologies are anticipated to play a vital role in the early detection and management of drug-resistant TB strains.
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