Project Title
Establishing a long-term observatory of the urban microbiome and antimicrobial resistance in Chile
Partner Organisations
Internal ID
1221209
Principal Investigator
JUAN ANTONIO UGALDE CASANOVA
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Item type:Publication, Reduced microbial diversity of the nasopharyngeal microbiome in household contacts with latent tuberculosis infection(2023) ;Cinthya Ruiz-Tagle ;Juan A. Ugalde ;Rodrigo Naves; Patricia García<jats:title>Abstract</jats:title><jats:p>The upper respiratory tract is an obliged pathway for respiratory pathogens and a healthy microbiota may support the host's mucosal immunity preventing infection. We analyzed the nasopharyngeal microbiome in tuberculosis household contacts (HHCs) and its association with latent tuberculosis infection (TBI). A prospective cohort of HHCs was established and latent TBI status was assessed by serial interferon-γ release assay (IGRA). Nasopharyngeal swabs collected at baseline were processed for 16S rRNA gene sequencing. The 82 participants included in the analysis were classified as: (a) non-TBI [IGRA negative at baseline and follow-up, no active TB (n = 31)], (b) pre-TBI [IGRA negative at baseline but converted to IGRA positive or developed active TB at follow-up (n = 16)], and (c) TBI [IGRA positive at enrollment (n = 35)]. Predominant phyla were <jats:italic>Actinobacteriota</jats:italic>, <jats:italic>Proteobacteria</jats:italic>, <jats:italic>Firmicutes</jats:italic> and <jats:italic>Bacteroidota</jats:italic>. TBI group had a lower alpha diversity compared to non-TBI (p<jats:sub>adj</jats:sub> = 0.04) and pre-TBI (p<jats:sub>adj</jats:sub> = 0.04). Only TBI and non-TBI had beta diversity differences (p<jats:sub>adj</jats:sub> = 0.035). Core microbiomes’ had unique genera, and genus showed differential abundance among groups. HHCs with established latent TBI showed reduced nasopharyngeal microbial diversity with distinctive taxonomical composition. Whether a pre-existing microbiome feature favors, are a consequence, or protects against <jats:italic>Mycobacterium tuberculosis</jats:italic> needs further investigation.</jats:p>Scopus© Citations 3 3 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Ceftazidime/avibactam resistance is associated with PER-3-producing ST309 lineage in Chilean clinical isolates of non-carbapenemase producing Pseudomonas aeruginosa(2024) ;Katherine D. Soto; ;UGALDE, JUAN ANTONIO ;Jorge Olivares PachecoValeria Quiroz<jats:sec><jats:title>Introduction</jats:title><jats:p>Ceftazidime/avibactam (CZA) is indicated against multidrug-resistant <jats:italic>Pseudomonas aeruginosa</jats:italic>, particularly those that are carbapenem resistant. CZA resistance in <jats:italic>P. aeruginosa</jats:italic> producing PER, a class A extended-spectrum β-lactamase, has been well documented <jats:italic>in vitro</jats:italic>. However, data regarding clinical isolates are scarce. Our aim was to analyze the contribution of PER to CZA resistance in non-carbapenemase-producing <jats:italic>P. aeruginosa</jats:italic> clinical isolates that were ceftazidime and/or carbapenem non-susceptible.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Antimicrobial susceptibility was determined through agar dilution and broth microdilution, while <jats:italic>bla</jats:italic><jats:sub>PER</jats:sub> gene was screened through PCR. All PER-positive isolates and five PER-negative isolates were analyzed through Whole Genome Sequencing. The mutational resistome associated to CZA resistance was determined through sequence analysis of genes coding for PBPs 1b, 3 and 4, MexAB-OprM regulators MexZ, MexR, NalC and NalD, AmpC regulators AmpD and AmpR, and OprD porin. Loss of <jats:italic>bla</jats:italic><jats:sub>PER-3</jats:sub> gene was induced in a PER-positive isolate by successive passages at 43°C without antibiotics. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Twenty-six of 287 isolates studied (9.1%) were CZA-resistant. Thirteen of 26 CZA-resistant isolates (50%) carried <jats:italic>bla</jats:italic><jats:sub>PER</jats:sub>. One isolate carried <jats:italic>bla</jats:italic><jats:sub>PER</jats:sub> but was CZA-susceptible. PER-producing isolates had significantly higher MICs for CZA, amikacin, gentamicin, ceftazidime, meropenem and ciprofloxacin than non-PER-producing isolates. All PER-producing isolates were ST309 and their <jats:italic>bla</jats:italic><jats:sub>PER-3</jats:sub> gene was associated to ISCR1, an insertion sequence known to mobilize adjacent DNA. PER-negative isolates were classified as ST41, ST235 (two isolates), ST395 and ST253. PER-negative isolates carried genes for narrow-spectrum β-lactamases and the mutational resistome showed that all isolates had one major alteration in at least one of the genes analyzed. Loss of <jats:italic>bla</jats:italic><jats:sub>PER-3</jats:sub> gene restored susceptibility to CZA, ceftolozane/tazobactam and other β-lactamsin the <jats:italic>in vitro</jats:italic> evolved isolate. </jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>PER-3-producing ST309 <jats:italic>P. aeruginosa</jats:italic> is a successful multidrug-resistant clone with <jats:italic>bla<jats:sub>PER-3</jats:sub></jats:italic> gene implicated in resistance to CZA and other β-lactams.</jats:p></jats:sec>Scopus© Citations 1 4 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, 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; ; ;Carmen VarelaCristina 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 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Multispecies emergence of dual blaKPC/NDM carbapenemase-producing Enterobacterales recovered from invasive infections in Chile(American Society for Microbiology, 2025-01-31); ;Camila Solar ;Jose R. W. Martínez; Valeria QuirozCarbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) represent a significant global threat. The emergence of dual CP-CRE is particularly alarming, as they can potentially compromise the efficacy of newer antibiotics, further decreasing therapeutic alternatives. Herein, we report the emergence of multiple species of CP-CRE recovered from invasive infections in Chile that simultaneously harbor and provide an in-depth genomic characterization of these worrisome pathogens. We collected carbapenem-resistant Enterobacterales (CRE) isolates from invasive infections over a 4-year period, across 11 healthcare centers in Chile. Bacterial species and the presence of carbapenemase genes were confirmed using MALDI-TOF and PCR assays, respectively. Antimicrobial susceptibility testing was conducted through disk diffusion and broth microdilution methods. Dual CP-CRE isolates were subjected to short- and long-read whole genome sequencing to perform a detailed genomic characterization of the isolates and of the mobile genetic elements harboring the enzymes. From a total of 1,335 CRE isolates, we observed an increase in the prevalence of CP-CRE, from 11% in 2019 to 38% in 2022. A total of 11 dual CP-CRE isolates were recovered, all of them harboringScopus© Citations 10 15