3Detailed genomic and structure-based analysis of a new coronavirus, namely 2019-nCoV, 2 4 1 9 2 1 9 3 author/funder. All rights reserved. No reuse allowed without permission.
Fluoroquinolone resistance in Salmonella has become increasingly prevalent in
recent years. To probe the molecular basis of this phenomenon, the genetic and
phenotypic features of fluoroquinolone resistant Salmonella strains isolated from
food samples were characterized. Among the 82 Salmonella strains tested,
resistance rate of the three front line antibiotics of ceftriaxone, ciprofloxacin and
azithromycin was 10%, 39% and 25% respectively, which is significantly higher than that
reported in other countries. Ciprofloxacin resistant strains typically exhibited
cross-resistance to multiple antibiotics including ceftriaxone, primarily due to the
presence of multiple PMQR genes and the blaCTX-M-65,
blaCTX-M-55
blaCMY-2 and blaCMY-72 elements. The
prevalence rate of the oqxAB and aac(6’)-Ib-cr genes were 91% and
75% respectively, followed by qnrS (66%), qnrB (16%) and qnrD (3%).
The most common PMQR combination observable was
aac(6’)-Ib-cr-oqxAB-qnrS2, which accounted for 50% of
the ciprofloxacin resistant strains. Interestingly, such isolates contained either no
target mutations or only a single gyrA mutation. Conjugation and hybridization
experiments suggested that most PMQR genes were located either in the chromosome or a
non-transferrable plasmid. To summarize, findings in this work suggested that PMQRs
greatly facilitate development of fluoroquinolone resistance in Salmonella by
abolishing the requirement of target gene mutations.
The recently discovered colistin resistance-encoding element, mcr-1, adds to the list of mobile resistance genes whose products rapidly erode the antimicrobial efficacy of not only the commonly used antibiotics, but also the last line agents of carbapenems and colistin. The relative prevalence of mcr-1-bearing strains in various ecological niches including 1,371 food samples, 480 animal faecal samples, 150 human faecal samples and 34 water samples was surveyed using a novel in-house method. Bacteria bearing mcr-1 were commonly detected in water (71% of samples), animal faeces (51%), food products (36%), and exhibited stable carriage in 28% of human subjects surveyed. Such strains, which exhibited variable antibiotic susceptibility profiles, belonged to various Enterobacteriaceae species, with Escherichia coli being the most dominant in each specimen type. The mcr-1 gene was detectable in the chromosome as well as plasmids of various sizes. Among these, two conjugative plasmids of sizes ca 33 and ca 60 kb were found to be the key vectors that mediated mcr-1 transmission in organisms residing in various ecological niches. The high mcr-1 carriage rate in humans found in this study highlights the importance of continued vigilance, careful antibiotic stewardship, and the development of new antimicrobials.
The epidemiological features of the newly emerged carbapenem-resistant hypervirulent
Klebsiella pneumoniae
(CR-HvKP) and its potential threat to human health are currently unknown. In this study, a total of 784
bla
KPC-2
-bearing CRKP strains collected from three hospitals located at different geographical locales in China during 2014–2017 were subjected to molecular typing, screening of virulence plasmid, string test and WGS (367/784 strains). The proportion of CRKP among all clinical
K. pneumoniae
strains increased sharply in China during 2014–2017. A large proportion (58%) of these CRKP strains were found to harbour a virulence-encoding plasmid, while only 13% of such strains exhibited a hypervirulent phenotype by string test and neutrophil assay. The lack of hypervirulent phenotype in virulent plasmid-bearing CRKP strains was found to be due to the mutation’s presence on
rmpA
and
rmpA2
genes, which rendered them non-functional, while some strains carrying wild type
rmpA
did not exhibit hypervirulent phenotype either suggesting that other factors might also contribute to the hypervirulence of CRKP. Phylogenetic and SNP analysis indicated that the transmission of these CRKP strains in China likely involved several major clones of ST11. Carriage of IncFII pSWU01-like,
bla
KPC-2
-bearing plasmid was found to be the major mechanism of carbapenem resistance in these CRKP strains. In conclusion, our data indicated that the prevalence of CRKP strains carrying the virulence plasmid has rapidly increased in China, while genetic markers were not correlated well with the hypervirulent phenotypes, which call for a better definition and screening for these truly hypervirulent CR-HvKP strains in clinical settings.
The rapid dissemination of non‐conjugative virulence plasmids among non‐K1/K2 types of Klebsiella pneumoniae poses an unprecedented threat to human health, yet the underlying mechanisms governing dissemination of such plasmids is unclear. In this study, a novel 68 581 bp IncFIA plasmid is discovered that can be fused to a hypervirulence‐encoding plasmid to form a hybrid conjugative virulence plasmid in conjugation experiments; such fusion events involve homologous recombination between a 241 bp homologous region located in each of the two plasmids. The fusion hypervirulence‐encoding plasmid can be conjugated to both classic and blaKPC‐2‐bearing carbapenem‐resistant K. pneumoniae strains through conjugation, enabling such strains to acquire the ability to express the hypervirulence phenotype. Dissemination of this fusion virulence plasmid will impose an enormous burden on current efforts to control and treat infections caused by multidrug resistant and hypervirulent K. pneumoniae.
Carbapenem-resistant and hypervirulent K. pneumoniae (CR-HvKP) strains that have emerged recently have caused infections of extremely high mortality in various countries. In this study, we discovered a conjugative plasmid that encodes carbapenem resistance and hypervirulence in a clinical ST86 K2 CR-HvKP, namely 17ZR-91. The conjugative plasmid (p17ZR-91-Vir-KPC) was formed by fusion of a non-conjugative pLVPK-like plasmid and a conjugative blaKPC-2-bearing plasmid and is present dynamically with two other non-fusion plasmids. Conjugation of p17ZR-91-Vir-KPC to other K. pneumoniae enabled them to rapidly express the carbapenem resistance and hypervirulence phenotypes. More importantly, genome analysis provided direct evidence that p17ZR-91-Vir-KPC could be directly transmitted from K2 CR-HvKP strain, 17ZR-91, to ST11 clinical K. pneumoniae strains to convert them into ST11 CR-HvKP strains, which explains the evolutionary mechanisms of recently emerged ST11 CR-HvKP strains.
This study aimed to characterize novel conjugative plasmids that encode transferable ciprofloxacin resistance in In this study, 157 nonduplicated isolates were recovered from food products, of which 55 were found to be resistant to ciprofloxacin. Interestingly, 37 of the 55 Cip isolates (67%) did not harbor any mutations in the quinolone resistance-determining regions (QRDR). Six isolates were shown to carry two novel types of conjugative plasmids that could transfer the ciprofloxacin resistance phenotype to J53 (azithromycin resistant [Azi]). The first type of conjugative plasmid belonged to the ∼110-kb IncFIB-type conjugative plasmids carrying -bearing and-bearing mobile elements. Transfer of the plasmid between and could confer a ciprofloxacin MIC of 1 to 2 μg/ml. The second type of conjugative plasmid belonged to ∼240-kb IncH1/IncF plasmids carrying a single PMQR gene, Importantly, this type of conjugative ciprofloxacin resistance plasmid could be detected in clinical isolates. The dissemination of these conjugative plasmids that confer ciprofloxacin resistance poses serious challenges to public health and infection control.
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