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  • 1
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    The Transcriptional Repressor SmvR Is Important for Decreased Chlorhexidine Susceptibility in Enterobacter cloacae Complex
    American Society for Microbiology ; 2019
    In:  Antimicrobial Agents and Chemotherapy Vol. 64, No. 1 ( 2019-12-20)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 64, No. 1 ( 2019-12-20)
    Kurzfassung: Major facilitator superfamily (MFS) efflux pumps have been shown to be important for bacterial cells to cope with biocides such as chlorhexidine (CHX), a widely used molecule in hospital settings. In this work, we evaluated the role of two genes, smvA and smvR , in CHX resistance in Enterobacter cloacae complex (ECC). smvA encodes an MFS pump whereas smvR , located upstream of smvA, codes for a TetR-type transcriptional repressor. To this aim, we constructed corresponding deletion mutants from the ATCC 13047 strain (CHX MIC, 2 mg/liter) as well as strains overexpressing smvA or smvR in both ATCC 13047 and three clinical isolates exhibiting elevated CHX MICs (16 to 32 mg/liter). Determination of MICs revealed that smvA played a modest role in CHX resistance, in contrast to smvR that modulated the ability of ECC to survive in the presence of CHX. In clinical isolates, the overexpression of smvR significantly reduced MICs of CHX (2 to 8 mg/liter). Sequence analyses of smvR and promoter regions pointed out substitutions in conserved regions. Moreover, transcriptional studies revealed that SmvR acted as a repressor of smvA expression even if no quantitative correlation between the level of smvA mRNA and MICs of CHX could be observed. On the other hand, overproduction of smvA was able to complement the lack of the major resistance-nodulation-cell division (RND) superfamily efflux pump AcrB and restored resistance to ethidium bromide and acriflavine. Although SmvA could expel biocides such as CHX, other actors, whose expression is under SmvR control, should play a critical role in ECC.
    Materialart: Online-Ressource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.01845-19
    RVK:
    XA 24552
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2019
    ZDB Id: 1496156-8
    SSG: 12
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
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    ramR Deletion in an Enterobacter hormaechei Isolate as a Consequence of Therapeutic Failure of Key Antibiotics in a Long-Term Hospitalized Patient
    American Society for Microbiology ; 2020
    In:  Antimicrobial Agents and Chemotherapy Vol. 64, No. 10 ( 2020-09-21)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 64, No. 10 ( 2020-09-21)
    Kurzfassung: Genome changes are central to the adaptation of bacteria, especially under antibiotic pressure. The aim of this study was to report phenotypic and genomic adaptations undergone by an Enterobacter hormaechei clinical strain that became highly resistant to key antimicrobials during a 4-month period in a patient hospitalized in an intensive care unit (ICU). All six clinical E. hormaechei strains isolated in one ICU-hospitalized patient have been studied. MICs regarding 17 antimicrobial molecules have been measured. Single nucleotide polymorphisms (SNPs) were determined on the sequenced genomes. The expression of genes involved in antibiotic resistance among Enterobacter cloacae complex strains were determined by reverse transcription-quantitative PCR (qRT-PCR). All the strains belonged to sequence type 66 and were distant by a maximum of nine SNPs. After 3 months of hospitalization, three strains presented a significant increase in MICs for ceftazidime, cefepime, temocillin, ertapenem, tigecycline, ciprofloxacin, and chloramphenicol. Those resistant strains did not acquire additional antibiotic resistance genes but harbored a 16-bp deletion in the ramR gene. This deletion led to upregulated expression of RamA, AcrA, AcrB, and TolC and downregulated expression of OmpF. The Δ ramR mutant harbored the same phenotype as the resistant clinical strains regarding tigecycline, chloramphenicol, and ciprofloxacin. The increased expression of RamA due to partial deletion in the ramR gene led to a cross-resistance phenotype by an increase of antibiotic efflux through the AcrAB-TolC pump and a decrease of antibiotic permeability by porin OmpF. ramR appears to be an important adaptative trait for E. hormaechei strains.
    Materialart: Online-Ressource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00962-20
    RVK:
    XA 24552
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2020
    ZDB Id: 1496156-8
    SSG: 12
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    A 10-year microbiological study of Pseudomonas aeruginosa strains revealed the circulation of populations resistant to both carbapenems and quaternary ammonium compounds
    Springer Science and Business Media LLC ; 2023
    In:  Scientific Reports Vol. 13, No. 1 ( 2023-02-14)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-02-14)
    Kurzfassung: Pseudomonas aeruginosa is one of the leading causes of healthcare-associated infections. For this study, the susceptibility profiles to antipseudomonal antibiotics and a quaternary ammonium compound, didecyldimethylammonium chloride (DDAC), widely used as a disinfectant, were established for 180 selected human and environmental hospital strains isolated between 2011 and 2020. Furthermore, a genomic study determined resistome and clonal putative relatedness for 77 of them. During the ten-year study period, it was estimated that 9.5% of patients’ strains were resistant to carbapenems, 11.9% were multidrug-resistant (MDR), and 0.7% were extensively drug-resistant (XDR). Decreased susceptibility (DS) to DDAC was observed for 28.0% of strains, a phenotype significantly associated with MDR/XDR profiles and from hospital environmental samples ( p   〈  0.0001). According to genomic analyses, the P. aeruginosa population unsusceptible to carbapenems and/or to DDAC was diverse but mainly belonged to top ten high-risk clones described worldwide by del Barrio-Tofiño et al. The carbapenem resistance appeared mainly due to the production of the VIM-2 carbapenemase (39.3%) and DS to DDAC mediated by MexAB-OprM pump efflux overexpression. This study highlights the diversity of MDR/XDR populations of P. aeruginosa which are unsusceptible to compounds that are widely used in medicine and hospital disinfection and are probably distributed in hospitals worldwide.
    Materialart: Online-Ressource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-023-29590-0
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 2615211-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
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    Unexpected Cell Wall Alteration-Mediated Bactericidal Activity of the Antifungal Caspofungin against Vancomycin-Resistant Enterococcus faecium
    American Society for Microbiology ; 2020
    In:  Antimicrobial Agents and Chemotherapy Vol. 64, No. 10 ( 2020-09-21)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 64, No. 10 ( 2020-09-21)
    Kurzfassung: Enterococcus faecium has become a major opportunistic pathogen with the emergence of vancomycin-resistant enterococci (VRE). As part of the gut microbiota, they have to cope with numerous stresses, including effects of antibiotics and other xenobiotics, especially in patients hospitalized in intensive care units (ICUs) who receive many medications. The aim of this study was to investigate the impact of the most frequently prescribed xenobiotics for ICU patients on fitness, pathogenicity, and antimicrobial resistance of the vanB -positive E. faecium Aus0004 reference strain. Several phenotypic analyses were carried out, and we observed that caspofungin, an antifungal agent belonging to the family of echinocandins, had an important effect on E. faecium growth in vitro . We confirmed this effect by electron microscopy and peptidoglycan analysis and showed that, even at a subinhibitory concentration (1/4× MIC, 8 mg/liter), caspofungin had an impact on cell wall organization, especially with respect to the abundance of some muropeptide precursors. By transcriptome sequencing (RNA-seq), it was also shown that around 20% of the transcriptome was altered in the presence of caspofungin, with 321 and 259 significantly upregulated and downregulated genes, respectively. Since the fungal target of caspofungin (i.e., β-1,3-glucan synthase) was absent in bacteria, the mechanistic pathway of caspofungin activity was investigated. The repression of genes involved in the metabolism of pyruvate seemed to have a drastic impact on bacterial cell viability, while a decrease of glycerol metabolism could explain the conformational modifications of peptidoglycan. This is the first report of caspofungin antibacterial activity against E. faecium , highlighting the potential impact of nonantibiotic xenobiotics against bacterial pathogens.
    Materialart: Online-Ressource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.01261-20
    RVK:
    XA 24552
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2020
    ZDB Id: 1496156-8
    SSG: 12
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    Unique Changes in the Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Unravel the Role of Respiratory Pathogens
    Elsevier BV ; 2023
    In:  CHEST ( 2023-8)
    Details
    In: CHEST, Elsevier BV, ( 2023-8)
    Materialart: Online-Ressource
    ISSN: 0012-3692
    URL: Article
    DOI: 10.1016/j.chest.2023.07.4219
    RVK:
    XA 36340
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2023
    ZDB Id: 2007244-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
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    Table_4.xlsx
    Frontiers Media SA ; 2021
    In:  Frontiers in Microbiology Vol. 12 ( 2021-6-25)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 12 ( 2021-6-25)
    Kurzfassung: Species belonging to Enterobacter cloacae complex have been isolated in numerous environments and samples of various origins. They are also involved in opportunistic infections in plants, animals, and humans. Previous prospection in Guadeloupe (French West Indies) indicated a high frequency of E. cloacae complex strains resistant to third-generation cephalosporins (3GCs) in a local lizard population ( Anolis marmoratus ), but knowledge of the distribution and resistance of these strains in humans and the environment is limited. The aim of this study was to compare the distribution and antibiotic susceptibility pattern of E. cloacae complex members from different sources in a “one health” approach and to find possible explanations for the high level of resistance in non-human samples. E. cloacae complex strains were collected between January 2017 and the end of 2018 from anoles, farm animals, local fresh produce, water, and clinical human samples. Isolates were characterized by the heat-shock protein 60 gene-fragment typing method, and whole-genome sequencing was conducted on the most frequent clusters (i.e., C-VI and C-VIII). The prevalence of resistance to 3GCs was relatively high (56/346, 16.2%) in non-human samples. The associated resistance mechanism was related to an AmpC overproduction; however, in human samples, most of the resistant strains (40/62) produced an extended-spectrum beta-lactamase. No relation was found between resistance in isolates from wild anoles (35/168) and human activities. Specific core-genome phylogenetic analysis highlighted an important diversity in this bacterial population and no wide circulation among the different compartments. In our setting, the mutations responsible for resistance to 3GCs, especially in ampD , were diverse and not compartment specific. In conclusion, high levels of resistance in non-human E. cloacae complex isolates are probably due to environmental factors that favor the selection of these resistant strains, and this will be explored further.
    Materialart: Online-Ressource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2021.628058
    DOI: 10.3389/fmicb.2021.628058.s001
    DOI: 10.3389/fmicb.2021.628058.s002
    DOI: 10.3389/fmicb.2021.628058.s003
    DOI: 10.3389/fmicb.2021.628058.s004
    DOI: 10.3389/fmicb.2021.628058.s005
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2021
    ZDB Id: 2587354-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
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    Exploring Cluster-Dependent Antibacterial Activities and Resistance Pathways of NOSO-502 and Colistin against Enterobacter cloacae Complex Species
    American Society for Microbiology ; 2022
    In:  Antimicrobial Agents and Chemotherapy Vol. 66, No. 11 ( 2022-11-15)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 66, No. 11 ( 2022-11-15)
    Kurzfassung: The Enterobacter cloacae complex (ECC) is a group of diverse environmental and clinically relevant bacterial species associated with a variety of infections in humans. ECC have emerged as one of the leading causes of nosocomial infections worldwide. The purpose of this paper is to evaluate the activity of NOSO-502 and colistin (CST) against a panel of ECC clinical isolates, including different Hoffmann’s clusters strains, and to investigate the associated resistance mechanisms. NOSO-502 is the first preclinical candidate of a novel antibiotic class, the odilorhabdins (ODLs). MIC 50 and MIC 90 of NOSO-502 against ECC are 1 μg/mL and 2 μg/mL, respectively, with a MIC range from 0.5 μg/mL to 32 μg/mL. Only strains belonging to clusters XI and XII showed decreased susceptibility to both NOSO-502 and CST while isolates from clusters I, II, IV, and IX were only resistant to CST. To understand this phenomenon, E. cloacae ATCC 13047 from cluster XI was chosen for further study. Results revealed that the two-component system ECL_01761-ECL_01762 (ortholog of CrrAB from Klebsiella pneumoniae ) induces NOSO-502 hetero-resistance by expression regulation of the ECL_01758 efflux pump component (ortholog of KexD from K. pneumoniae ) which could compete with AcrB to work with the multidrug efflux pump proteins AcrA and TolC. In E. cloacae ATCC 13047, CST-hetero-resistance is conferred via modification of the lipid A by addition of 4-amino-4-deoxy- l -arabinose controlled by PhoPQ. We identified that the response regulator ECL_01761 is also involved in this resistance pathway by regulating the expression of the ECL_01760 membrane transporter.
    Materialart: Online-Ressource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/aac.00776-22
    RVK:
    XA 24552
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2022
    ZDB Id: 1496156-8
    SSG: 12
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
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    Temocillin Resistance in the Enterobacter cloacae Complex Is Conferred by a Single Point Mutation in BaeS, Leading to Overexpression of the AcrD Efflux Pump
    American Society for Microbiology ; 2023
    In:  Antimicrobial Agents and Chemotherapy Vol. 67, No. 6 ( 2023-06-15)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 67, No. 6 ( 2023-06-15)
    Kurzfassung: The Enterobacter cloacae complex (ECC) has become a major opportunistic pathogen with antimicrobial resistance issues. Temocillin, an “old” carboxypenicillin that is remarkably stable toward β-lactamases, has been used as an alternative for the treatment of multidrug-resistant ECC infections. Here, we aimed at deciphering the never-investigated mechanisms of temocillin resistance acquisition in Enterobacterales . By comparative genomic analysis of two clonally related ECC clinical isolates, one susceptible (Temo_S [MIC of 4 mg/L]) and the other resistant (Temo_R [MIC of 32 mg/L] ), we found that they differed by only 14 single-nucleotide polymorphisms, including one nonsynonymous mutation (Thr175Pro) in the two-component system (TCS) sensor histidine kinase BaeS. By site-directed mutagenesis in Escherichia coli CFT073, we demonstrated that this unique change in BaeS was responsible for a significant (16-fold) increase in temocillin MIC. Since the BaeSR TCS regulates the expression of two resistance-nodulation-cell division (RND)-type efflux pumps (namely, AcrD and MdtABCD) in E. coli and Salmonella , we demonstrated by quantitative reverse transcription-PCR that mdtB , baeS , and acrD genes were significantly overexpressed (15-, 11-, and 3-fold, respectively) in Temo_R. To confirm the role of each efflux pump in this mechanism, multicopy plasmids harboring mdtABCD or acrD were introduced into either Temo_S or the reference strain E. cloacae subsp. cloacae ATCC 13047. Interestingly, only the overexpression of acrD conferred a significant increase (from 8- to 16-fold) of the temocillin MIC. Altogether, we have shown that temocillin resistance in the ECC can result from a single BaeS alteration, likely resulting in the permanent phosphorylation of BaeR and leading to AcrD overexpression and temocillin resistance through enhanced active efflux.
    Materialart: Online-Ressource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/aac.00358-23
    RVK:
    XA 24552
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2023
    ZDB Id: 1496156-8
    SSG: 12
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
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    Good immunogenicity of GBM strain inactivated hepatitis A vaccine in healthy male adults
    Elsevier BV ; 1995
    In:  Vaccine Vol. 13, No. 2 ( 1995-1), p. 220-224
    Details
    In: Vaccine, Elsevier BV, Vol. 13, No. 2 ( 1995-1), p. 220-224
    Materialart: Online-Ressource
    ISSN: 0264-410X
    URL: Article
    DOI: 10.1016/0264-410X(95)93140-5
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 1995
    ZDB Id: 1468474-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
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    Phenotypic and proteomic approaches of the response to iron-limited condition in Staphylococcus lugdunensis
    Springer Science and Business Media LLC ; 2020
    In:  BMC Microbiology Vol. 20, No. 1 ( 2020-12)
    Details
    In: BMC Microbiology, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)
    Kurzfassung: Staphylococcus lugdunensis is a coagulase-negative Staphylococcus part of the commensal skin flora but emerge as an important opportunistic pathogen. Because iron limitation is a crucial stress during infectious process, we performed phenotypic study and compared proteomic profiles of this species incubated in absence and in presence of the iron chelator 2,2′-dipyridyl (DIP). Results No modification of cell morphology nor cell wall thickness were observed in presence of DIP. However iron-limitation condition promoted biofilm formation and reduced the ability to cope with oxidative stress (1 mM H 2 O 2 ). In addition, S. lugdunensis N920143 cultured with DIP was significantly less virulent in the larvae of Galleria mellonella model of infection than that grown under standard conditions. We verified that these phenotypes were due to an iron limitation by complementation experiments with FeSO 4 . By mass spectrometry after trypsin digestion, we characterized the first iron-limitation stress proteome in S. lugdunensis . Among 1426 proteins identified, 349 polypeptides were differentially expressed. 222 were more and 127 less abundant in S. lugdunensis incubated in iron-limitation condition, and by RT-qPCR, some of the corresponding genes have been shown to be transcriptionally regulated. Our data revealed that proteins involved in iron metabolism and carriers were over-expressed, as well as several ABC transporters and polypeptides linked to cell wall metabolism. Conversely, enzymes playing a role in the oxidative stress response (especially catalase) were repressed. Conclusions This phenotypic and global proteomic study allowed characterization of the response of S. lugdunensis to iron-limitation. We showed that iron-limitation promoted biofilm formation, but decrease the oxidative stress resistance that may, at least in part, explained the reduced virulence of S. lugdunensis observed under low iron condition.
    Materialart: Online-Ressource
    ISSN: 1471-2180
    URL: Article
    DOI: 10.1186/s12866-020-02016-x
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2020
    ZDB Id: 2041505-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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