Analysis of mcr-1-containing sequences identified a common ∼2,607-bp DNA segment that in many cases is flanked on one or both ends by ISApl1 We present evidence that mcr-1 is mobilized by an ISApl1 ...composite transposon which has, in some cases, subsequently lost one or both copies of ISApl1 We also show that mcr-1 can be mobilized in some circumstances by a single upstream copy of ISApl1 in conjunction with the remnants of a downstream ISApl1.
Multidrug resistance in
has become a worrying issue that is increasingly observed in human but also in veterinary medicine worldwide.
is intrinsically susceptible to almost all clinically relevant ...antimicrobial agents, but this bacterial species has a great capacity to accumulate resistance genes, mostly through horizontal gene transfer. The most problematic mechanisms in
correspond to the acquisition of genes coding for extended-spectrum β-lactamases (conferring resistance to broad-spectrum cephalosporins), carbapenemases (conferring resistance to carbapenems), 16S rRNA methylases (conferring pan-resistance to aminoglycosides), plasmid-mediated quinolone resistance (PMQR) genes (conferring resistance to fluoroquinolones), and
genes (conferring resistance to polymyxins). Although the spread of carbapenemase genes has been mainly recognized in the human sector but poorly recognized in animals, colistin resistance in
seems rather to be related to the use of colistin in veterinary medicine on a global scale. For the other resistance traits, their cross-transfer between the human and animal sectors still remains controversial even though genomic investigations indicate that extended-spectrum β-lactamase producers encountered in animals are distinct from those affecting humans. In addition,
of animal origin often also show resistances to other-mostly older-antimicrobial agents, including tetracyclines, phenicols, sulfonamides, trimethoprim, and fosfomycin. Plasmids, especially multiresistance plasmids, but also other mobile genetic elements, such as transposons and gene cassettes in class 1 and class 2 integrons, seem to play a major role in the dissemination of resistance genes. Of note, coselection and persistence of resistances to critically important antimicrobial agents in human medicine also occurs through the massive use of antimicrobial agents in veterinary medicine, such as tetracyclines or sulfonamides, as long as all those determinants are located on the same genetic elements.
Antibiotic resistance is a threat to human and animal health worldwide, and key measures are required to reduce the risks posed by antibiotic resistance genes that occur in the environment. These ...measures include the identification of critical points of control, the development of reliable surveillance and risk assessment procedures, and the implementation of technological solutions that can prevent environmental contamination with antibiotic resistant bacteria and genes. In this Opinion article, we discuss the main knowledge gaps, the future research needs and the policy and management options that should be prioritized to tackle antibiotic resistance in the environment.
A colistin-resistant Escherichia coli strain was recovered from a patient with a diabetic foot infection in Brazil. Whole-genome analysis revealed that the E. coli isolate belonged to the widespread ...sequence type (ST) 101 and harbored the mcr-1 gene on an IncX4 plasmid that was highly similar to mcr-1-bearing IncX4 plasmids that were recently identified in Enterobacteriaceae from food, animal, and human samples recovered on different continents. These results suggest that self-transmissible IncX4-type plasmids may represent promiscuous plasmids contributing to the intercontinental spread of the mcr-1 gene.
The use of antibiotics has enabled the successful treatment of bacterial infections, saving the lives and improving the health of many patients worldwide. However, the emergence and spread of ...antimicrobial resistance (AMR) has been highlighted as a global threat by different health organizations, and pathogens resistant to antimicrobials cause substantial morbidity and death. As resistance to multiple drugs increases, novel and effective therapies as well as prevention strategies are needed. In this Review, we discuss evidence that vaccines can have a major role in fighting AMR. Vaccines are used prophylactically, decreasing the number of infectious disease cases, and thus antibiotic use and the emergence and spread of AMR. We also describe the current state of development of vaccines against resistant bacterial pathogens that cause a substantial disease burden both in high-income countries and in low- and medium-income countries, discuss possible obstacles that hinder progress in vaccine development and speculate on the impact of next-generation vaccines against bacterial infectious diseases on AMR.
Antibiotic use is the main driver in the emergence of antibiotic resistance. Another unexplored possibility is that resistance evolves coincidentally in response to other selective pressures. We show ...that selection in the absence of antibiotics can coselect for decreased susceptibility to several antibiotics. Thus, genetic adaptation of bacteria to natural environments may drive resistance evolution by generating a pool of resistance mutations that selection could act on to enrich resistant mutants when antibiotic exposure occurs.
All cellular membranes have the functionality of generating and maintaining the gradients of electrical and electrochemical potentials. Such potentials were generally thought to be an essential but ...homeostatic contributor to complex bacterial behaviors. Recent studies have revised this view, and we now know that bacterial membrane potential is dynamic and plays signaling roles in cell–cell interaction, adaptation to antibiotics, and sensation of cellular conditions and environments. These discoveries argue that bacterial membrane potential dynamics deserve more attention. Here, we review the recent studies revealing the signaling roles of bacterial membrane potential dynamics. We also introduce basic biophysical theories of the membrane potential to the microbiology community and discuss the needs to revise these theories for applications in bacterial electrophysiology.
Bacterial membrane potential is dynamic, with the ability to hyperpolarize and depolarize.The dynamics of bacterial membrane potential mediate signaling at the single-cell and biofilm levels.Bacterial electrophysiology is different from neural electrophysiology because of the size of bacteria and their membrane structure.Techniques have been developed and utilized to measure bacterial membrane potential quantitatively and temporally.
Abstract
The growing prevalence of deadly microbes with resistance to previously life-saving drug therapies is a dire threat to human health. Detection of low abundance pathogen sequences remains a ...challenge for metagenomic Next Generation Sequencing (NGS). We introduce FLASH (Finding Low Abundance Sequences by Hybridization), a next-generation CRISPR/Cas9 diagnostic method that takes advantage of the efficiency, specificity and flexibility of Cas9 to enrich for a programmed set of sequences. FLASH-NGS achieves up to 5 orders of magnitude of enrichment and sub-attomolar gene detection with minimal background. We provide an open-source software tool (FLASHit) for guide RNA design. Here we applied it to detection of antimicrobial resistance genes in respiratory fluid and dried blood spots, but FLASH-NGS is applicable to all areas that rely on multiplex PCR.
Two adjacent colistin resistance gene variants, termed
and
-like, were identified in the chromosome of an
isolate obtained from retail chicken meat. The variants showed 95.20% and 84.19% nucleotide ...sequence identity, respectively, to
from porcine
Functional cloning indicated that only
conferred polymyxin resistance in both
and
The
-like segment was also observed in other
species, including
,
, and
.
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