The widespread use of antibiotics is selecting for a variety resistance mechanisms that seriously challenge our ability to treat bacterial infections. Resistant bacteria can be selected at the high concentrations used therapeutically, but what role much lower antibiotic present in many environments plays selection remains largely unclear. Here we show using highly sensitive competition experiments resistant occurs extremely low concentrations. Thus, three clinically important antibiotics,...

How sublethal levels of antibiotics and heavy metals select for clinically important multidrug resistance plasmids is largely unknown. Carriage generally confers substantial fitness costs, implying that the plasmid-carrying bacteria to be maintained in population, plasmid cost needs balanced by a selective pressure conferred by, example, or metals. We studied effects low on maintenance 220-kbp extended-spectrum β-lactamase (ESBL) identified hospital outbreak Klebsiella pneumoniae Escherichia...

ObjectivesThe biological fitness cost of antibiotic resistance is a key parameter in determining the rate appearance and spread antibiotic-resistant bacteria. We identified mutations conferring nitrofurantoin examined their effect on clinical Escherichia coli isolates.

To characterize the complete sequence, horizontal spread and stability of CTX-M-15-encoding multiresistance plasmid a Klebsiella pneumoniae strain involved in large nosocomial outbreak.The 220 kbp pUUH239.2 was completely sequenced using 454 technology. The conjugational host range, conjugation frequencies, fitness cost carriage were studied vitro. Conjugational during outbreak assessed retrospectively by multiplex PCR screening, restriction fragment length polymorphism PFGE.Plasmid encodes...

ABSTRACT Tigecycline is a glycylcycline antibiotic active against multidrug-resistant bacterial pathogens. The objectives of our study were to examine the potential Tet(A), Tet(K), Tet(M), and Tet(X) tetracycline resistance proteins acquire mutations causing tigecycline determine how this affects earlier classes tetracyclines. Mutations in all four tet genes caused significant increase MIC Escherichia coli , strains expressing mutant Tet(A) variants reached clinically relevant MICs (2...

An important mechanism for generation of new genes is by duplication-divergence existing genes. Duplication-divergence includes several different submodels, such as subfunctionalization where after accumulation neutral mutations the original function distributed between two partially functional and complementary genes, neofunctionalization a evolves in one duplicated copies while old maintained another copy. The likelihood these mechanisms depends on longevity state, which turn fitness cost...

By providing the bacterial cell with protection against several antibiotics at once, multiresistance plasmids have an evolutionary advantage in situations where antibiotic treatments are common, such as hospital environments. However, resistance can also impose fitness costs on bacterium absence of antibiotics, something that may limit their success. The underlying mechanisms and possible contribution genes to still largely not understood. Here, we specifically investigated plasmid-borne...

Abstract Antimicrobial resistance (AMR) is an increasing problem worldwide, and new treatment options for bacterial infections are direly needed. Engineered probiotics show strong potential in treating or preventing infections. However, one concern with the use of live bacteria risk acquiring genes encoding AMR virulence factors through horizontal gene transfer (HGT), transformation probiotic into a superbug. Therefore, we developed engineered CRISPR-Cas9 system that protects from transfer....

Between May and December 2005, 64 multidrug‐resistant isolates of Klebsiella pneumoniae were detected from patients admitted to Uppsala University Hospital. This represented a dramatic increase in ESBL‐producing K. compared previous years. To investigate the epidemiology characterize resistance mechanisms isolates, study was initiated. Antibiotic susceptibility determined by means Etest disc diffusion method. Extended‐spectrum beta‐lactamase (ESBL) production identified clavulanic acid...

Abstract Multidrug resistance was found in 22.7% of Escherichia coli isolates from bird samples Bangladesh; 30% produced extended-spectrum β-lactamases, including clones CTX-M genes among wild and domestic birds. Unrestricted use antimicrobial drugs feed for birds the spread to large reservoir Bangladesh are growing problems.

To stepwise select tigecycline-resistant Escherichia coli mutants in vitro, determine the mutation rates, identify resistance mechanisms, level and cross-resistance to other antibiotic classes, evaluate fitness costs of tigecycline mechanisms investigate if same invitro-identified target genes were mutated clinical isolates. Spontaneous with reduced susceptibility selected on agar plates supplemented tigecycline. Resistance levels evaluated by performing MIC assays determining rates using...

The worldwide spread of ESBL-producing Enterobacteriaceae has led to an increased use carbapenems, the group β-lactams with broadest spectrum activity. Bacterial resistance carbapenems is mainly due acquired carbapenemases or a combination ESBL production and reduced drug influx via loss outer-membrane porins. Here, we have studied development carbapenem in Escherichia coli absence β-lactamases.We selected mutants high-level through repeated serial passage presence increasing concentrations...

Clonally derived bacterial populations exhibit significant genotypic and phenotypic diversity that contribute to fitness in rapidly changing environments. Here, we show serial passage of Salmonella enterica serovar Typhimurium LT2 (StLT2) broth, or within a mouse host, results selection an evolved population inhibits the growth ancestral cells by direct contact. Cells each gain ability express deploy cryptic "orphan" toxin encoded rearrangement hotspot (rhs) locus. The Rhs orphan is gene...

Abstract Bacterial plasmids are extensively involved in the rapid global spread of antibiotic resistance. We here present an assay, based on optical DNA mapping single nanofluidic channels, which provides detailed information about a bacterial isolate. In experiment, we obtain number different sample, size each plasmid, barcode that can be used to identify and trace plasmid interest carries specific resistance gene. Gene identification is done using CRISPR/Cas9 loaded with guide-RNA (gRNA)...

Carbapenem resistant Enterobacteriaceae (CRE) are a threat to public health globally, yet the role of environment in epidemiology CRE remains elusive. Given that wild birds can acquire CRE, likely from foraging anthropogenically impacted areas, and may aid maintenance dissemination environment, spatiotemporal comparison isolates different regions timepoints be useful for elucidating epidemiological information. Thus, we characterized genomic diversity fecal samples opportunistically...

Ertapenem resistance is increasing in Enterobacteriaceae. The production of extended-spectrum β-lactamases (ESBLs) and reduced expression outer membrane porins are major mechanisms ertapenem-resistant Klebsiella pneumoniae. Less known ertapenem Escherichia coli. aim this study was to explore the impact ESBL E. coli on antibacterial activity ertapenem.Two strains, with without production, were exposed vitro for 48 h at concentrations simulating human pharmacokinetics conventional higher...

Time lapse antibiotic susceptibility investigation.

To investigate the influence of plasmid-borne β-lactamases on evolution spontaneous carbapenem resistance in Escherichia coli and fitness costs associated with resistance. Stepwise selection carbapenem-resistant mutants or without extended-spectrum β-lactamase (ESBL)-encoding plasmid pUUH239.2 was performed. Mutation rates mutational pathways to were determined. In vitro-selected constructed characterized regarding MICs carbapenems, porin expression profiles, growth presence mutations porins...

ABSTRACT Members of the Enterobacteriaceae with extended-spectrum beta-lactamases (ESBLs) CTX-M type have disseminated rapidly in recent years and become a threat to public health. In parallel expansion, consumption widespread use silver-containing products has increased. To determine carriage rates silver resistance genes different Escherichia coli populations, presence three ( silE , silP silS ) encoding CTX-M-, TEM-, SHV-type enzymes were explored E. isolates human n = 105) avian 111)...

Abstract Background Identification of pathogens is crucial to efficiently treat and prevent bacterial infections. However, existing diagnostic techniques are slow or have a too low resolution for well-informed clinical decisions. Methods In this study, we developed an optical DNA mapping-based method strain-level typing simultaneous plasmid characterisation. For the typing, different taxonomical resolutions were examined cultivated pure Escherichia coli Klebsiella pneumoniae samples used...

Infections caused by Extended spectrum β-lactamase (ESBL)-producing E. coli are an emerging global problem, threatening the effectiveness of extensively used β-lactam antibiotics. ESBL dissemination is facilitated plasmids, transposons, and other mobile elements. We have characterized plasmid content ESBL-producing from human urinary tract infections. Ten diverse isolates were selected; they had unrelated pulsed-field gel electrophoresis (PFGE) types (<90% similarity), geographically...

The presence and frequency of multiresistant bacteria in wild birds act as indicators the environmental contamination antibiotic resistance. To explore rate mediated by Escherichia coli, 150 fecal samples from brown-headed gull (Chroicocephalus brunnicephalus) 8 water Bay Bengal area were collected, cultured, tested for susceptibility. Special attention was paid to extended-spectrum beta-lactamase (ESBL)-producing isolates, which further characterized genetically. Antibiotic resistance found...