Lyhnemose9184

lindamycin, and population demographics.

HIV-1 group O (HIV-1/O) is one of the four HIV-1 groups and is endemic in Cameroon, representing 1% of HIV-1 infections in the population. Around 50% of the strains of this group naturally show a mutation (Y181C) providing them with resistance to NNRTIs and making therapeutic management more difficult. Today, the WHO recommends the use of integrase strand transfer inhibitors (INSTIs) as first-line treatment. Bictegravir and cabotegravir are the two most recent INSTIs. Because of the genetic polymorphism of HIV-1/O, studies are required to evaluate their phenotypic susceptibility to these two drugs.

We performed a phenotypic study on a large panel including 41 HIV-1/O clinical isolates and other rare non-group M HIV-1 (2 HIV-1/N and 1 HIV-1/P) to evaluate in vitro susceptibility to bictegravir and cabotegravir.

The results showed an overall susceptibility of non-group M strains to the two drugs compared with HIV-1 group M. There was no difference between the mean (min-max) IC50 of HIV-1/M [1.86 (0.93-4.12) and 5.24 (1.76-12.41) nM for bictegravir and cabotegravir, respectively] and HIV-1/non-M [2.17 (0.03-9.47) and 4.88 (0.02-15.64) nM for bictegravir and cabotegravir, respectively]. However, we found a significant difference between IC50 values for bictegravir and cabotegravir in the whole panel (P value < 0.001).

This study has shown encouraging results regarding the clinical use of these drugs in HIV-1/non-M-infected patients, which will need to be confirmed with clinical data.

This study has shown encouraging results regarding the clinical use of these drugs in HIV-1/non-M-infected patients, which will need to be confirmed with clinical data.

PBP4, a low-molecular-weight PBP in Staphylococcus aureus, is not considered to be a classical mediator of β-lactam resistance. CK-586 ic50 Previous studies carried out by our group with laboratory strains of S. aureus demonstrated the ability of PBP4 to produce β-lactam resistance through mutations associated with the pbp4 promoter and/or gene. Recent studies of β-lactam-resistant clinical isolates of S. aureus have reported similar mutations associated with pbp4.

To determine if pbp4-associated mutations reported among clinical strains of S. aureus mediate β-lactam resistance.

The pbp4 promoters and genes bearing mutations from clinical isolates were cloned into a heterologous host. Reporter, growth and Bocillin assays were performed to assess their role in β-lactam resistance. X-ray crystallography was used to obtain acyl-enzyme intermediate structures of the WT and mutant PBP4 with nafcillin and cefoxitin.

Of the five strains that contained pbp4 promoter mutations, three strains exhibited enhanced expression of PBP4. The R200L mutation in pbp4 resulted in increased survival in the presence of the β-lactams nafcillin and cefoxitin. Further, introduction of either a promoter or a gene mutation into the genome of a WT host increased the ability of the strains to resist the action of β-lactams. The four high-resolution X-ray structures presented demonstrate the binding pose of the β-lactams tested and provide hints for further drug development.

Mutations associated with the pbp4 promoter and pbp4 gene altered protein activity and mediated β-lactam resistance among the clinically isolated strains that were studied.

Mutations associated with the pbp4 promoter and pbp4 gene altered protein activity and mediated β-lactam resistance among the clinically isolated strains that were studied.

The SmeVWX efflux pump of Stenotrophomonas maltophilia contributes to menadione (MD) tolerance and resistance to chloramphenicol, quinolones and tetracycline. The components of the SmeVWX efflux pump are encoded by a five-gene operon, smeU1VWU2X. We have previously demonstrated that the smeU1VWU2X operon is intrinsically unexpressed and inducibly expressed by MD via a SoxR- and SmeRv-involved regulatory circuit in S. maltophilia KJ. We also inferred that there should be other regulator(s) involved in MD-mediated smeU1VWU2X expression in addition to SoxR and SmeRv.

To identify novel regulator(s) involved in the regulation of MD-mediated smeU1VWU2X expression and elucidate the regulatory circuit.

A possible regulator candidate involved in the regulation of MD-mediated smeU1VWU2X expression was identified by a homologue search using the helix-turn-helix domain of SmeRv as a query. Gene expression was assessed using the promoter-xylE transcriptional fusion assay and quantitative RT-PCR. The impact of the regulator on SmeVWX pump-mediated functions was investigated via mutant construction and functional tests (antibiotic susceptibility and MD tolerance).

AzoR (Smlt3089), a LysR-type transcriptional regulator, was investigated. In unstressed logarithmically grown cells, AzoR was abundantly expressed and functioned as a repressor, inhibiting the expression of the smeU1VWU2X operon. MD challenge attenuated azoR expression, thus derepressing the expression of the smeU1VWU2X operon in S. maltophilia KJ. AzoR down-regulation-mediated smeU1VWU2X expression was observed in quinolone-resistant and SmeVWX-overexpressing S. maltophilia clinical isolates.

AzoR negatively regulates the expression of the smeU1VWU2X operon and SmeVWX pump-mediated antibiotic resistance in S. maltophilia.

AzoR negatively regulates the expression of the smeU1VWU2X operon and SmeVWX pump-mediated antibiotic resistance in S. maltophilia.

The COVID-19 epidemic has spread rapidly within aged-care facilities (ACFs), where the infection-fatality ratio is high. It is therefore urgent to evaluate the efficiency of infection prevention and control (IPC) measures in reducing SARS-CoV-2 transmission.

We analysed the COVID-19 outbreaks that took place between March and May 2020 in 12 ACFs using reverse transcription-polymerase chain reaction (RT-PCR) and serological tests for SARS-CoV-2 infection. Using maximum-likelihood approaches and generalized linear mixed models, we analysed the proportion of infected residents in ACFs and identified covariates associated with the proportion of infected residents.

The secondary-attack risk was estimated at 4.1%, suggesting a high efficiency of the IPC measures implemented in the region. Mask wearing and the establishment of COVID-19 zones for infected residents were the two main covariates associated with lower secondary-attack risks.

Wearing masks and isolating potentially infected residents appear to be associated with a more limited spread of SARS-CoV-2 in ACFs.