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Author: search.filters.author.Juan A. UgaldeSubject: search.filters.subject.article

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    Whole-genome sequencing reveals changes in genomic diversity and distinctive repertoires of T3SS and T6SS effector candidates in Chilean clinical Campylobacter strains
    (2023)
    Assaf Katz
    ;
    Lorena Porte  
    ;
    WEITZEL, THOMAS  
    ;
    Carmen Varela
    ;
    Cristina Muñoz-Rehbein
    <jats:p><jats:italic>Campylobacter</jats:italic> is the leading cause of bacterial gastroenteritis worldwide and an emerging and neglected pathogen in South America. This zoonotic pathogen colonizes the gastrointestinal tract of a wide range of mammals and birds, with poultry as the most important reservoir for human infections. Apart from its high morbidity rates, the emergence of resistant strains is of global concern. The aims of this work were to determine genetic diversity, presence of antimicrobial resistance determinants and virulence potential of <jats:italic>Campylobacter</jats:italic> spp. isolated from patients with acute gastrointestinal disease at ‘Clinica Alemana’, Santiago de Chile. The study considered the isolation of <jats:italic>Campylobacter</jats:italic> spp., from stool samples during a 20-month period (January 2020 to September 2021). We sequenced (NextSeq, Illumina) and performed an in-depth analysis of the genome sequences of 88 <jats:italic>Campylobacter jejuni</jats:italic> and 2 <jats:italic>Campylobacter</jats:italic> coli strains isolated from clinical samples in Chile. We identified a high genetic diversity among C. je<jats:italic>juni</jats:italic> strains and the emergence of prevalent clonal complexes, which were not identified in our previous reports. While ~40% of strains harbored a mutation in the gyrA gene associated with fluoroquinolone resistance, no macrolide-resistance determinants were detected. Interestingly, gene clusters encoding virulence factors such as the T6SS or genes associated with long-term sequelae such as Guillain-Barré syndrome showed lineage-relatedness. In addition, our analysis revealed a high degree of variability regarding the presence of fT3SS and T6SS effector proteins in comparison to type strains 81-176, F38011, and NCTC 11168 and 488. Our study provides important insights into the molecular epidemiology of this emerging foodborne pathogen. In addition, the differences observed regarding the repertoire of fT3SS and T6SS effector proteins could have an impact on the pathogenic potential and transmissibility of these Latin American isolates, posing another challenge in characterizing the infection dynamics of this emergent and neglected bacterial pathogen.</jats:p>
      29Scopus© Citations 8
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    Role of the multi-drug efflux systems on the baseline susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam in clinical isolates of non-carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa
    (2022)
    María José Contreras-Gómez
    ;
    José R. W. Martinez
    ;
    RIVAS JIMENEZ, LINA MARIA  
    ;
    Juan A. Ugalde
    ;
    Roberto Riquelme-Neira  
    <jats:p>Carbapenem-resistant <jats:italic>Pseudomonas aeruginosa</jats:italic> (CRPA) is one of the pathogens that urgently needs new drugs and new alternatives for its control. The primary strategy to combat this bacterium is combining treatments of beta-lactam with a beta-lactamase inhibitor. The most used combinations against <jats:italic>P. aeruginosa</jats:italic> are ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T). Although mechanisms leading to CZA and C/T resistance have already been described, among which are the resistance-nodulation-division (RND) efflux pumps, the role that these extrusion systems may play in CZA, and C/T baseline susceptibility of clinical isolates remains unknown. For this purpose, 161 isolates of non-carbapenemase-producing (Non-CP) CRPA were selected, and susceptibility tests to CZA and C/T were performed in the presence and absence of the RND efflux pumps inhibitor, Phenylalanine-arginine β-naphthylamide (PAβN). In the absence of PAβN, C/T showed markedly higher activity against Non-CP-CRPA isolates than observed for CZA. These results were even more evident in isolates classified as extremely-drug resistant (XDR) or with difficult-to-treat resistance (DTR), where CZA decreased its activity up to 55.2% and 20.0%, respectively, whereas C/T did it up to 82.8% (XDR), and 73.3% (DTR). The presence of PAβN showed an increase in both CZA (37.6%) and C/T (44.6%) activity, and 25.5% of Non-CP-CRPA isolates increased their susceptibility to these two combined antibiotics. However, statistical analysis showed that only the C/T susceptibility of Non-CP-CRPA isolates was significantly increased. Although the contribution of RND activity to CZA and C/T baseline susceptibility was generally low (two-fold decrease of minimal inhibitory concentrations [MIC]), a more evident contribution was observed in a non-minor proportion of the Non-CP-CRPA isolates affected by PAβN [CZA: 25.4% (15/59); C/T: 30% (21/70)]. These isolates presented significantly higher MIC values for C/T. Therefore, we conclude that RND efflux pumps are participating in the phenomenon of baseline susceptibility to CZA and, even more, to C/T. However, the genomic diversity of clinical isolates is so great that deeper analyzes are necessary to determine which elements are directly involved in this phenomenon.</jats:p>
      1Scopus© Citations 7
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    Scopus© Citations 7  1
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    Scopus© Citations 14  2