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1.
C R Biol ; 345(1): 37-56, 2022 May 11.
Article in English | MEDLINE | ID: mdl-35787619

ABSTRACT

In 2022, the burden of cholera-an acute watery diarrheal disease caused by Vibrio cholerae serogroup O1 (or more rarely O139) bacteria, which produce cholera toxin-remains high in many African and Asian countries. In the last few years, microbial genomics has made it possible to define the bacterial populations responsible for cholera more precisely. It has been shown that the current, seventh pandemic is due to a single lineage with a reservoir in the countries of the Bay of Bengal (India and Bangladesh). There have been several transmissions of the causal agent of cholera from this region to Africa, Asia and Latin America, suggesting a human-to-human transmission of the disease. Microbial genetics can help to fight this scourge by providing insight into cholera epidemiology and through its use in disease monitoring, thereby contributing to the achievement of the World Health Organization's goal of reducing cholera deaths by 90% by 2030.


En 2022, de nombreux pays d'Afrique et d'Asie restent des foyers épidémiques de choléra, maladie diarrhéique causée par la bactérie Vibrio cholerae de sérogroupe O1 (ou plus rarement O139) produisant la toxine cholérique. La génomique microbienne a permis ces dernières années de mieux définir les populations bactériennes responsables du choléra. Il a ainsi été montré qu'il n'existait qu'une seule lignée génétique de Vibrio cholerae O1 responsable de la septième pandémie dont le réservoir se situe dans la région du golfe du Bengale (Inde et Bangladesh). Plusieurs évènements de transmission de l'agent du choléra vers l'Afrique, l'Europe ou l'Amérique latine ont été identifiés et suggèrent une transmission interhumaine de la maladie. Les données issues des travaux de génomique microbienne ainsi que son utilisation pour la surveillance globale du choléra vont permettre de mieux lutter contre ce fléau et participer à l'objectif de l'Organisation mondiale de la Santé de réduire de 90 % les décès dus à cette maladie en 2030.


Subject(s)
Cholera , Vibrio cholerae , Asia/epidemiology , Bangladesh/epidemiology , Cholera/etiology , Cholera/microbiology , Genomics , Humans , Vibrio cholerae/genetics
3.
Article in English | MEDLINE | ID: mdl-30275089

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) infection has increased in recent years among cystic fibrosis (CF) patients. Linezolid (LZD) is one of the antistaphylococcal antibiotics widely used in this context. Although LZD resistance is rare, it has been described as often associated with long-term treatments. Thirteen MRSA strains isolated over 5 years from one CF patient were studied for LZD resistance emergence and subjected to whole-genome sequencing (WGS). Resistance emerged after three 15-day LZD therapeutic regimens over 4 months. It was associated with the mutation of G to T at position 2576 (G2576T) in all 5 rrl copies, along with a very high MIC (>256 mg/liter) and a strong increase in the generation time. Resistant strains isolated during the ensuing LZD therapeutic regimens and until 13 months after LZD stopped harbored only 3 or 4 mutated rrl copies, associated with lower MICs (8 to 32 mg/liter) and low to moderate generation time increases. Despite these differences, whole-genome sequencing allowed us to determine that all isolates, including the susceptible one isolated before LZD treatment, belonged to the same lineage. In conclusion, LZD resistance can emerge rapidly in CF patients and persist without linezolid selective pressure in colonizing MRSA strains belonging to the same lineage.


Subject(s)
Cystic Fibrosis/microbiology , Host-Pathogen Interactions/genetics , Linezolid/therapeutic use , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Infections/microbiology , Drug Resistance, Bacterial/drug effects , Drug Resistance, Bacterial/genetics , Evolution, Molecular , Genome, Bacterial , Host-Pathogen Interactions/drug effects , Humans , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Phylogeny , Polymorphism, Single Nucleotide , Staphylococcal Infections/drug therapy , Time Factors
5.
J Pediatr ; 200: 30-37.e2, 2018 09.
Article in English | MEDLINE | ID: mdl-29793870

ABSTRACT

OBJECTIVES: To establish the reference values, diagnostic accuracy, and effect of various factors on cell count in intubated preterm neonates subjected to nonbronchoscopic bronchoalveolar lavage. STUDY DESIGN: This prospective, cross-sectional, blinded study included preterm neonates ventilated for any reason who underwent nonbronchoscopic bronchoalveolar lavage if they had not previously received postnatal antibiotics or steroids. Lavage was performed before surfactant replacement, if any. A gentle ventilation policy was applied. Pneumonia was diagnosed using clinical criteria, without considering cell count. Investigators performing cell counts were blinded to the clinical data. RESULTS: There were 276 neonates enrolled; 36 had congenital or ventilator-associated pneumonia. In the 240 noninfected babies, median neutrophil count increased significantly after the first 2 days of ventilation (day 1, 2 cells per field [IQR, 0.0-9.5 cells per field]; day 2, 2 cells per field [IQR, 0-15 cells per field]; day 3, 20 cells per field [IQR, 2-99 cells per field]; day 4, 15 cells per field [IQR, 2-96 cells per field]; P < .0001). No significant difference was seen over time in infected babies. Multivariate analysis indicated pneumonia (standardized ß = 0.134; P = .033) and the time spent under mechanical ventilation before nonbronchoscopic bronchoalveolar lavage as factors significantly influencing neutrophil count (standardized ß = 0.143; P = .027). Neutrophil count was correlated with the duration of ventilation (rho = 0.28; P <.001). Neutrophil counts were higher in infected (24 cells/field [IQR, 5-78] cells/field) than in noninfected babies (4 cells/field [IQR, 1-24 cells/field]; P <.001) and had an moderate reliability for pneumonia within the first 2 days of ventilation (area under the curve, 0.745; (95% CI, 0.672-0.810; P = .002). CONCLUSIONS: We provide reference values for airway neutrophil counts in ventilated preterm neonates. Bronchoalveolar lavage neutrophils significantly increase after 2 days of ventilation. Neutrophil count has moderate accuracy to diagnose pneumonia, but only within the first 2 days of ventilation.


Subject(s)
Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage/methods , Infant, Premature , Pneumonia, Ventilator-Associated/diagnosis , Respiration, Artificial/adverse effects , Bronchoscopy , Cell Count , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Infant, Newborn , Male , Prospective Studies , Reproducibility of Results
6.
Microb Drug Resist ; 23(4): 462-467, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27754824

ABSTRACT

Linezolid (LZD) has arisen as an alternative treatment in diabetic foot osteitis due to staphylococci. LZD resistance selection is difficult and involved various molecular mechanisms. As a better knowledge of those mechanisms could be beneficial for pathogenic strains' screening, we simulated in vitro the spontaneous mutagenesis process that leads to LZD-resistant strains from two Staphylococcus epidermidis strains responsible for monomicrobial diabetic foot osteitis. LZD high resistance was selected for both strains, with the same timeline of mutation appearance. Mutation in L3 protein (G152D) occurred first and quickly, but did not cause phenotypically detectable resistance or fitness cost. It was later followed by different 23S rRNA mutations (G2505A, G2447T), leading this time to detectable resistance (minimum inhibitory concentration [MIC] ≥8 mg/L). This phenomenon underlies the difficulty of resistance selection in coagulase-negative staphylococci (CoNS). This study is the first description of G2505A mutation in CoNS. Various phenotypical impacts were observed depending on strain and mutation: (i) fitness cost of G2505A and G2447T mutations; (ii) loss of erythromycin resistance concomitantly with L3 mutation selection; (iii) correlation between number of mutated rrl copies and LZD resistance level for G2447T. In conclusion, the risk of selection of high-level LZD-resistant S. epidermidis strains is weak, but does exist. It could probably appear in case of long-term treatment and be favored in the case of a pre-existing mutation in L3 ribosomal protein. Thus, broad screening conditions for pathogenic strains should probably be considered.


Subject(s)
DNA, Ribosomal/genetics , Drug Resistance, Bacterial/genetics , Linezolid/pharmacology , RNA, Ribosomal, 23S/genetics , Ribosomal Proteins/genetics , Staphylococcus epidermidis/genetics , Anti-Bacterial Agents/pharmacology , Diabetic Foot/microbiology , Genetic Fitness , Humans , Microbial Sensitivity Tests , Osteitis/microbiology , Phenotype , Point Mutation , Protein Biosynthesis/drug effects , Ribosomal Protein L3 , Ribosomes/drug effects , Ribosomes/genetics , Risk , Selection, Genetic , Staphylococcal Infections/microbiology , Staphylococcus epidermidis/drug effects , Staphylococcus epidermidis/metabolism
7.
Antiviral Res ; 128: 1-6, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26826441

ABSTRACT

The emergence of herpes simplex virus (HSV) resistance to current antiviral drugs, that all target the viral DNA polymerase, constitutes a major obstacle to antiviral treatment effectiveness of HSV infections, especially in immunocompromised patients. A novel and promising class of inhibitors of the HSV UL5/UL52 helicase-primase (HP) complex has been reported to hinder viral replication with a high potency. In this study, we describe the low natural polymorphism (interstrain identity >99.1% at both nucleotide and amino acid levels) of HSV HP complex subunits pUL5 and pUL52 among 64 HSV (32 HSV-1 and 32 HSV-2) clinical isolates, and we show that the HSV resistance profile to the first-line antiviral drug acyclovir (ACV) does not impact on the natural polymorphism of HSV HP complex. Genotypic tools and polymorphism data concerning HSV HP complex provided herein will be useful to detect drug resistance mutations in a relevant time frame when HP inhibitors (HPIs), i.e., amenamevir and pritelivir, will be available in medical practice.


Subject(s)
Antiviral Agents/therapeutic use , DNA Helicases/antagonists & inhibitors , DNA Helicases/genetics , DNA Primase/antagonists & inhibitors , DNA Primase/genetics , Drug Resistance, Viral , Herpesvirus 2, Human/genetics , Oxadiazoles/therapeutic use , Pyridines/therapeutic use , Simplexvirus/genetics , Thiazoles/therapeutic use , Viral Proteins/antagonists & inhibitors , Viral Proteins/genetics , Acyclovir/therapeutic use , Herpesvirus 2, Human/drug effects , Herpesvirus 2, Human/isolation & purification , Humans , Immunocompromised Host , Polymorphism, Genetic , Simplexvirus/drug effects , Simplexvirus/isolation & purification , Sulfonamides
8.
AIDS ; 28(14): 2160-2, 2014 Sep 10.
Article in English | MEDLINE | ID: mdl-25265081

ABSTRACT

The distribution and evolution of X4/R5 viral tropism during HIV-2 infection remains unknown. HIV-2 tropism was assessed in 83 antiretroviral-experienced patients with virological failure. Tropism was predicted as X4 in 58% of patients and was associated with a CD4 cell count of less than 100 cells/µl, and with a higher number of drug resistance mutations. This high prevalence of X4 virus might compromise the use of CCR5 inhibitors, currently mostly considered in HIV-2 salvage therapy of highly pretreated patients.


Subject(s)
CCR5 Receptor Antagonists/therapeutic use , Cyclohexanes/therapeutic use , HIV Infections/immunology , HIV-2 , Receptors, CCR5/drug effects , Triazoles/therapeutic use , Viral Tropism , CD4 Lymphocyte Count , Disease Progression , Drug Resistance, Viral , Genotype , HIV Infections/drug therapy , HIV Infections/genetics , HIV-2/physiology , Humans , Maraviroc , Prevalence , Retrospective Studies , Viral Load
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