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1.
J Med Chem ; 63(17): 9168-9180, 2020 09 10.
Article in English | MEDLINE | ID: mdl-32790310

ABSTRACT

Antimicrobial peptides (AMPs) are amphipathic molecules displaying broad-spectrum bactericidal activity, providing opportunities to develop a new generation of antibiotics. However, their use is limited either by poor metabolic stability or by high hemolytic activity. We herein addressed the potential of thiazole-based γ-peptide oligomers named ATCs as tunable scaffolds to design polycationic AMP mimetics. Knowing the side chain distribution along the backbone, we rationally designed facially amphiphilic sequences with bactericidal effect in the micromolar range. Since no hemolytic activity was detected up to 100 µM, this class of compounds has shown the potential for therapeutic development.


Subject(s)
Anti-Bacterial Agents/chemistry , Antimicrobial Cationic Peptides/chemistry , Thiazoles/chemistry , Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Drug Design , Erythrocytes/cytology , Erythrocytes/drug effects , Erythrocytes/metabolism , Fungi/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Hemolysis/drug effects , Humans , Microbial Sensitivity Tests
2.
Am J Infect Control ; 47(12): 1510-1512, 2019 12.
Article in English | MEDLINE | ID: mdl-31277997

ABSTRACT

The investigation of an outbreak of Pseudomonas aeruginosa urinary tract infections after ambulatory cystoscopies identified a damaged cystoscope contaminated by P aeruginosa and acting as a relay object. This outbreak urges us not to trivialize urinary tract infections occurring after an elective cystoscopy. Patients should be advised to signal the occurrence of urologic symptoms after urologic exploration.


Subject(s)
Cross Infection/epidemiology , Cystoscopy/adverse effects , Disease Outbreaks , Pseudomonas Infections/epidemiology , Pseudomonas aeruginosa/pathogenicity , Urinary Tract Infections/epidemiology , Aged , Aged, 80 and over , Cross Infection/diagnosis , Cross Infection/etiology , Cross Infection/transmission , France/epidemiology , Hospitals , Humans , Male , Middle Aged , Outpatients , Pseudomonas Infections/diagnosis , Pseudomonas Infections/etiology , Pseudomonas Infections/transmission , Pseudomonas aeruginosa/isolation & purification , Urinary Tract Infections/diagnosis , Urinary Tract Infections/etiology , Urinary Tract Infections/transmission
3.
Infect Genet Evol ; 70: 131-139, 2019 06.
Article in English | MEDLINE | ID: mdl-30790700

ABSTRACT

Entomopathogenic nematodes (EPNs) form specific mutualistic associations with bioluminescent enterobacteria. In Heterorhabditidis indica, Ochrobactrum spp. was identified beside the symbiont Photorhabdus luminescens but its involvement in the symbiotic association in the EPNs remains unclear. This study describe the population structure and the diversity in Ochrobactrum natural populations isolated from EPNs in the Caribbean basin in order to question the existence of EPN-specialized clones and to gain a better insight into Ochrobactrum-EPNs relationships. EPN-associated Ochrobactrum and Photorhabdus strains were characterized by multi-locus sequence typing, Pulsed-Field Gel Electrophoresis fingerprinting and phenotypic traits. Population study showed the absence of EPN-specialized clones in O. intermedium and O. anthropi but suggested the success of some particular lineages. A low level of genetic and genomic diversification of Ochrobactrum isolated from the natural population of Caribbean nematodes was observed comparatively to the diversity of human-associated Ochrobactrum strains. Correspondences between Ochrobactrum and P. luminescens PFGE clusters have been observed, particularly in the case of nematodes from Dominican Republic and Puerto Rico. O. intermedium and O. anthropi associated to EPNs formed less biofilm than human-associated strains. These results evoke interactions between Ochrobactrum and the EPN symbiotic system rather than transient contamination. The main hypothesis to investigate is a toxic/antitoxic relationship because of the ability of Ochrobactrum to resist to antimicrobial and toxic compounds produced by Photorhabdus.


Subject(s)
Nematoda/microbiology , Ochrobactrum/genetics , Animals , Caribbean Region/epidemiology , Dominican Republic/epidemiology , Genetics, Population , Humans , Multilocus Sequence Typing , Photorhabdus , Phylogeny , Puerto Rico/epidemiology , Symbiosis
4.
Eur J Pediatr ; 178(4): 505-513, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30671695

ABSTRACT

In the context of a 3-month extended-spectrum beta-lactamase-producing Klebsiella pneumonia (ESBL-KP) outbreak in a neonatal care center (NCC), hygiene practices and hospital environment were investigated. ESBL-KP strains isolated from patients and environment were compared by molecular typing. The density of incidence of multi-drug-resistant bacteria (MDRB) was calculated from January 2014 to September 2016. The 3-month ESBL-KP outbreak involved 19 patients. Clinical strains from the 19 patients displayed the same molecular profile between them, and with a strain isolated from an incubator after cleaning. Furthermore, 52.4% of incubator mattresses were positive for diverse pathogens. Hygiene practices were acceptable except for external practitioners and parents. In addition to classical infection control (IC) measures, the replacement of mattresses and the improvement of incubators disinfection stopped the outbreak. The protocol of disinfection was revised and microbiological control was implemented. A significant decrease of MDRB incidence was concomitant (p value = 0.03219) but 3 months later, MDRB incidence increased again.Conclusion: This investigation highlighted incubators and mattresses as critical materials associated to infectious risk in NCC. NCC and IC teams should implement efficient protocol for incubators disinfection and monitoring. What is Known: • Environment in neonatal intensive care units is often suspected as reservoir for Enterobacteriaceae outbreaks but is scarcely investigated. • Incubators and mattresses offer wet and warm conditions suitable for pathogens multiplication, but microbiological survey is not performed routinely for assessing bacterial contamination. What is New: • Incubators and mattresses serve as reservoir for pathogens and relay in outbreak. • An infection control protocol associating efficient disinfection and microbiology analysis is proposed.


Subject(s)
Beds/adverse effects , Incubators, Infant/adverse effects , Infection Control/methods , Klebsiella Infections/etiology , Cross Infection/etiology , Cross Infection/prevention & control , Disease Outbreaks/prevention & control , Drug Resistance, Multiple , Female , Humans , Infant , Infant, Newborn , Intensive Care Units, Neonatal/standards , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/isolation & purification , Klebsiella pneumoniae/pathogenicity , Male , beta-Lactam Resistance , beta-Lactamases/metabolism
5.
Infect Genet Evol ; 65: 104-106, 2018 11.
Article in English | MEDLINE | ID: mdl-30030207

ABSTRACT

While typing methods are increasingly refined, the sampling of bacteria to be typed in healthcare-associated infection context retains less attention. Through 2 emblematic cases of in-hospital transmission of extensively drug-resistant bacteria producing carbapenemases, we demonstrate the impact of colony sampling in typing results. Because of intra-population diversity, typing several colonies of same species and resistotype was needed to fully track the transmission among patients. Bacterial population studies could better decipher transmission routes of healthcare-associated bacteria, thereby improving outbreak control.


Subject(s)
Bacteria/classification , Bacteria/genetics , Bacterial Proteins/genetics , Genetic Variation , Genetics, Population , Multilocus Sequence Typing , beta-Lactamases/genetics , Bacteria/enzymology , Bacterial Infections/epidemiology , Bacterial Infections/microbiology , Bacterial Proteins/biosynthesis , Biodiversity , Cross Infection/epidemiology , Cross Infection/microbiology , Humans , beta-Lactamases/biosynthesis
7.
PLoS One ; 9(1): e83376, 2014.
Article in English | MEDLINE | ID: mdl-24465379

ABSTRACT

Ochrobactrum intermedium is considered as an emerging human environmental opportunistic pathogen with mild virulence. The distribution of isolates and sequences described in literature and databases showed frequent association with human beings and polluted environments. As population structures are related to bacterial lifestyles, we investigated by multi-locus approach the genetic structure of a population of 65 isolates representative of the known natural distribution of O. intermedium. The population was further surveyed for genome dynamics using pulsed-field gel electrophoresis and genomics. The population displayed a clonal epidemic structure with events of recombination that occurred mainly in clonal complexes. Concerning biogeography, clones were shared by human and environments and were both cosmopolitan and local. The main cosmopolitan clone was genetically and genomically stable, and grouped isolates that all harbored an atypical insertion in the rrs. Ubiquitism and stability of this major clone suggested a clonal succes in a particular niche. Events of genomic reduction were detected in the population and the deleted genomic content was described for one isolate. O. intermedium displayed allopatric characters associated to a tendancy of genome reduction suggesting a specialization process. Considering its relatedness with Brucella, this specialization might be a commitment toward pathogenic life-style that could be driven by technological selective pressure related medical and industrial technologies.


Subject(s)
Ecosystem , Evolution, Molecular , Genome, Bacterial/genetics , Ochrobactrum/genetics , Technology , Base Sequence , Cluster Analysis , DNA, Bacterial/genetics , Databases, Genetic , Electrophoresis, Gel, Pulsed-Field , Humans , Likelihood Functions , Multilocus Sequence Typing , Ochrobactrum/classification , Ochrobactrum/physiology , Phylogeny
9.
J Bacteriol ; 193(10): 2608-18, 2011 May.
Article in English | MEDLINE | ID: mdl-21398532

ABSTRACT

The genus Agrobacterium includes plant-associated bacteria and opportunistic human pathogens. Taxonomy and nomenclature within the genus remain controversial. In particular, isolates of human origin were all affiliated with the species Agrobacterium (Rhizobium) radiobacter, while phytopathogenic strains were designated under the synonym denomination Agrobacterium tumefaciens. In order to study the relative distribution of Agrobacterium strains according to their origins, we performed a multilocus sequence-based analysis (MLSA) on a large collection of 89 clinical and environmental strains from various origins. We proposed an MLSA scheme based on the partial sequence of 7 housekeeping genes (atpD, zwf, trpE, groEL, dnaK, glnA, and rpoB) present on the circular chromosome of A. tumefaciens C58. Multilocus phylogeny revealed that 88% of the clinical strains belong to genovar A7, which formed a homogeneous population with linkage disequilibrium, suggesting a low rate of recombination. Comparison of genomic fingerprints obtained by pulsed-field gel electrophoresis (PFGE) showed that the strains of genovar A7 were epidemiologically unrelated. We present genetic evidence that genovar A7 may constitute a human-associated population distinct from the environmental population. Also, phenotypic characteristics, such as culture at 42°C, agree with this statement. This human-associated population might represent a potential novel species in the genus Agrobacterium.


Subject(s)
Bacterial Typing Techniques , Multilocus Sequence Typing , Phylogeny , Rhizobium/classification , Rhizobium/genetics , Bacterial Proteins/genetics , Cluster Analysis , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Electrophoresis, Gel, Pulsed-Field , Environmental Microbiology , Genotype , Gram-Negative Bacterial Infections/microbiology , Humans , Molecular Sequence Data , Polymorphism, Genetic , Sequence Analysis, DNA , Sequence Homology
10.
BMC Microbiol ; 9: 267, 2009 Dec 18.
Article in English | MEDLINE | ID: mdl-20021660

ABSTRACT

BACKGROUND: Ochrobactrum anthropi is a versatile bacterial species with strains living in very diverse habitats. It is increasingly recognized as opportunistic pathogen in hospitalized patients. The population biology of the species particularly with regard to the characteristics of the human isolates is being investigated. To address this issue, we proposed a polyphasic approach consisting in Multi-Locus Sequence Typing (MLST), multi-locus phylogeny, genomic-based fingerprinting by pulsed-field gel electrophoresis (PFGE) and antibiotyping. RESULTS: We tested a population of 70 O. anthropi clinical (n = 43) and environmental (n = 24) isolates as well as the type strain O. anthropi ATCC49188T and 2 strains of Ochrobactrum lupini and Ochrobactrum cytisi isolated from plant nodules. A Multi-Locus Sequence Typing (MLST) scheme for O. anthropi is proposed here for the first time. It was based on 7 genes (3490 nucleotides) evolving mostly by neutral mutations. The MLST approach suggested an epidemic population structure. A major clonal complex corresponded to a human-associated lineage since it exclusively contained clinical isolates. Genomic fingerprinting separated isolates displaying the same sequence type but it did not detect a population structure that could be related to the origin of the strains. None of the molecular method allowed the definition of particular lineages associated to the host-bacteria relationship (carriage, colonisation or infection). Antibiotyping was the least discriminative method. CONCLUSION: The results reveal a human-associated subpopulation in our collection of strains. The emergence of this clonal complex was probably not driven by the antibiotic selective pressure. Therefore, we hypothesise that the versatile species O. anthropi could be considered as a human-specialized opportunistic pathogen.


Subject(s)
Bacterial Typing Techniques , DNA Fingerprinting , Ochrobactrum anthropi/classification , Ochrobactrum anthropi/genetics , Cluster Analysis , Electrophoresis, Gel, Pulsed-Field , Environmental Microbiology , Genotype , Gram-Negative Bacterial Infections/microbiology , Humans , Molecular Sequence Data , Ochrobactrum anthropi/isolation & purification , Plant Diseases/microbiology , Polymorphism, Genetic , Ribotyping , Sequence Analysis, DNA
11.
Int J Syst Evol Microbiol ; 57(Pt 5): 1007-1013, 2007 May.
Article in English | MEDLINE | ID: mdl-17473249

ABSTRACT

Three novel Gram-negative, non-fermenting aerobic bacilli were isolated from human clinical samples. They shared more than 99.8 % of the 16S rRNA gene nucleotide positions. The strains were related to Ochrobactrum intermedium with about 97.48 % 16S rRNA gene sequence similarity. In 16S rRNA gene-, dnaK- and rpoB-based phylogenies, the strains were grouped in a lineage that was distinct from other Ochrobactrum species in the family Brucellaceae. Fatty acid composition, polar lipids, quinone system, DNA-DNA relatedness, genome organization, and physiological and biochemical data differentiated these isolates from recognized species of the genus Ochrobactrum. The three clinical strains therefore represent a novel species within the genus Ochrobactrum, for which the name Ochrobactrum pseudintermedium sp. nov., is proposed. The type strain is ADV31(T) (=CIP 109116(T)=DSM 17490(T)). The DNA G+C content of strain ADV31(T) was 54.5 mol%.


Subject(s)
Gram-Negative Bacterial Infections/microbiology , Ochrobactrum/classification , Ochrobactrum/isolation & purification , Bacterial Proteins/genetics , Bacterial Typing Techniques , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , DNA-Directed RNA Polymerases/metabolism , Fatty Acids/analysis , Genes, rRNA/genetics , Humans , Membrane Lipids/analysis , Molecular Sequence Data , Ochrobactrum/chemistry , Ochrobactrum/physiology , Phylogeny , Quinones/analysis , RNA, Bacterial/genetics , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Sequence Homology, Nucleic Acid
12.
Electrophoresis ; 26(15): 2898-907, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15995979

ABSTRACT

The alpha-proteobacterial genus Ochrobactrum groups together organisms that display varied life-styles, such as free-living bacteria, members of rhizosphere and soil, nitrogen-fixing bacteria in plant nodules, xenobiotic-degrading bacteria, colonizers of nematodes and insects, and opportunistic human pathogens. The genomes of nine strains of Ochrobactrum anthropi and eight strains of Ochrobactrum intermedium were analyzed by pulsed-field gel electrophoresis of the whole genome and of I-CeuI digestion fragments. All isolates and type strains of O. anthropi and O. intermedium possessed two high-molecular-weight circular replicons identified as two independent chromosomes on the basis of 16S rDNA hybridization. The genome of the type strain of Ochrobactrum tritici, Ochrobactrum grignonense, and Ochrobactrum gallinifaecis also contained two circular chromosomes. The megaplasmid content was highly variable even among strains in the same species, leading to whole-genome sizes that ranged from 5.060 to 8.300 Mbp and from 4.690 to 7.680 Mbp for O. anthropi and O. intermedium, respectively. This exceptional level of genomic diversity could be related to the adaptability of Ochrobactrum spp. to various ecological niches.


Subject(s)
Chromosomes, Bacterial , Genetic Variation , Genome, Bacterial , Ochrobactrum/genetics , Electrophoresis, Gel, Pulsed-Field , Ochrobactrum anthropi/genetics , Replicon
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