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Geographic divergence of methicillin-resistant Staphylococcus aureus ST5-SCCmecI in the aftermath of a major earthquake and tsunami: impact of a plasmid harboring heavy metal resistance genes
(American Society for Microbiology, 2025-04-09)
Jose R. W. Martínez
;
Manuel Alcalde-Rico
;
Estefanía Jara-Videla
;
Jinnethe Reyes
;
Lina P. Carvajal
(MRSA) is a major public health menace. The global spread of MRSA is characterized by successive waves of epidemic clones dominating specific geographical regions. The acquisition of genes encoding resistance to heavy metals (HMRGs) is thought to be a key feature in the geographic divergence of MRSA. However, the cause-effect relationship between the presence of HMRGs and the divergence of MRSA clones remains to be clarified. In this study, we assessed the role that HMRGs may have played in the evolutionary divergence of the MRSA ST5-SCC <jats:italic>mec</jats:italic> I lineage in Latin America. We conducted a genomic characterization of 113 MRSA clinical isolates from six Latin American healthcare centers, including 53 isolates collected from two cities in Chile (Santiago and Concepción). We found a plasmid (pSCL4752) harboring arsenic, cadmium, and mercury resistance genes in 65% ( <jats:italic>n</jats:italic> = 71) of the ST5-SCC <jats:italic>mec</jats:italic> I isolates. We also observed a geographic divergence associated with the presence of pSCL4752 in Chilean isolates, with a higher frequency in isolates from Concepción (88%) compared to Santiago (29%). Interestingly, a molecular clock analysis revealed that this divergence occurred in the aftermath of an 8.8 Mw earthquake and tsunami that struck the Concepción area in 2010. Moreover, our results demonstrate that the carriage of pSCL4752 can be beneficial or detrimental for ST5-SCC <jats:italic>mec</jats:italic> I isolates, depending on the environmental availability of these heavy metals. Our results suggest that the divergence of the ST5-SCC <jats:italic>mec</jats:italic> I MRSA lineage in Latin America could have been fostered by environmental disasters and influenced by the presence/absence of HMRGs harbored in a plasmid. </jats:p> <jats:sec> <jats:title>IMPORTANCE</jats:title> <jats:p> Methicillin-resistant <jats:italic>Staphylococcus aureus</jats:italic> (MRSA) is a major cause of life-threatening infections worldwide and a growing public health concern. The rise of antibiotic-resistant bacteria, such as MRSA, is often linked to genetic adaptations that enhance their survival. Our research sheds light on how environmental changes, such as those triggered by a natural disaster, can influence the evolution and geographic spread of a highly resistant MRSA lineage in Latin America. We identified a plasmid carrying genes for resistance to arsenic, cadmium, and mercury, which was associated with the geographic divergence of the ST5-SCC <jats:italic>mec</jats:italic> I MRSA lineage, with striking differences in its prevalence between regions affected by a major earthquake and tsunami. By linking environmental events to pathogen evolution, our study highlights the role of ecological pressures in the spread of MRSA. These findings emphasize the need to integrate environmental monitoring into public health strategies to better understand the global challenge of antimicrobial resistance.
4
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Multispecies emergence of dual blaKPC/NDM carbapenemase-producing Enterobacterales recovered from invasive infections in Chile
(American Society for Microbiology, 2025-01-31)
QUESILLE VILLALOBOS, ANA MARIA
;
Camila Solar
;
Jose R. W. Martínez
;
RIVAS JIMENEZ, LINA MARIA
;
Valeria Quiroz
Carbapenemase-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 harboring
Scopus© Citations 10 15
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Performance of the VITEK® MS system for the identification of filamentous fungi in a microbiological laboratory in Chile
(Public Library of Science (PLoS), 2024-12-23)
PORTE TORRE, LORENA ISABEL
;
Rodrigo Cruz
;
Pérez Villa, Inia
;
Carmen Varela
;
Cristina Díaz
<jats:p>Filamentous fungi are an emergent cause of severe infections in immunocompromised patients. Timely and accurate identification is crucial to initiate appropriate therapy. Traditional identification methods are time-consuming, labor-intensive, and operator-dependent. Matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry is a rapid and easy-to-perform identification method. The effectiveness of a commercial MALDI-TOF MS platform to identify filamentous fungi in a clinical laboratory was evaluated. The study included 67 fungal isolates from 35 species/species complexes, which were identified and confirmed in mycology reference laboratories; 32 derived from clinical samples, 34 from strain collections and one was an ATCC strain. The study used the VITEK<jats:sup>®</jats:sup> MS system (v3.2.0 database), after sample extraction by VITEK<jats:sup>®</jats:sup> MS Mould Kit. Results were classified as “correct species”, “correct species complex”, “correct genus”and “no identification”. VITEK<jats:sup>®</jats:sup> MS correctly identified 91.0% of isolates (58.2% to species, 29.9% to species complex, and 1.5% to genus level only). In 82%, the result matched the species/species complex identified by reference methods. No misidentifications were observed. The kit was rapid and easy to use. In conclusion, the VITEK<jats:sup>®</jats:sup> MS system showed a high capability to accurately identify filamentous fungi in a clinical laboratory.</jats:p>
1
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Salmonella enterica Serovar Abony Outbreak Caused by Clone of Reference Strain WDCM 00029, Chile, 2024
(Centers for Disease Control and Prevention (CDC), 2025-01)
Alejandro Piña-Iturbe
;
Diego Fredes-García
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Patricia García
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PORTE TORRE, LORENA ISABEL
;
Timothy J. Johnson
Scopus© Citations 1 1
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Dynamics of the MRSA Population in a Chilean Hospital: a Phylogenomic Analysis (2000–2016)
(2023)
José R. W. Martínez
;
Paul J. Planet
;
Maria Spencer-Sandino
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RIVAS JIMENEZ, LINA MARIA
;
Ahmed M. Moustafa
<jats:p> Methicillin-resistant <jats:named-content content-type="genus-species">Staphylococcus aureus</jats:named-content> (MRSA) is a major public health pathogen that disseminates through the emergence of successful dominant clones in specific geographic regions. Knowledge of the dissemination and molecular epidemiology of MRSA in Latin America is scarce and is largely based on small studies or more limited typing techniques that lack the resolution to represent an accurate description of the genomic landscape. </jats:p>
Scopus© Citations 6 4
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Antibiotic Consumption During the Coronavirus Disease 2019 Pandemic and Emergence of Carbapenemase-Producing <i>Klebsiella pneumoniae</i> Lineages Among Inpatients in a Chilean Hospital: A Time-Series Study and Phylogenomic Analysis
(2023)
Kasim Allel
;
Anne Peters
;
José Conejeros
;
José R W Martínez
;
Maria Spencer-Sandino
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>The impact of coronavirus disease 2019 (COVID-19) on antimicrobial use (AU) and resistance has not been well evaluated in South America. These data are critical to inform national policies and clinical care.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>At a tertiary hospital in Santiago, Chile, between 2018 and 2022, subdivided into pre- (3/2018–2/2020) and post–COVID-19 onset (3/2020–2/2022), we evaluated intravenous AU and frequency of carbapenem-resistant Enterobacterales (CRE). We grouped monthly AU (defined daily doses [DDD]/1000 patient-days) into broad-spectrum β-lactams, carbapenems, and colistin and used interrupted time-series analysis to compare AU during pre- and post-pandemic onset. We studied the frequency of carbapenemase-producing (CP) CRE and performed whole-genome sequencing analyses of all carbapenem-resistant (CR) Klebsiella pneumoniae (CRKpn) isolates collected during the study period.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P &lt; .001), 50.9 to 110.1 (P &lt; .001), and 4.1 to 13.3 (P &lt; .001) for broad-spectrum β-lactams, carbapenems, and colistin, respectively. The frequency of CP-CRE increased from 12.8% pre–COVID-19 to 51.9% after pandemic onset (P &lt; .001). The most frequent CRE species in both periods was CRKpn (79.5% and 76.5%, respectively). The expansion of CP-CRE harboring blaNDM was particularly noticeable, increasing from 40% (n = 4/10) before to 73.6% (n = 39/53) after pandemic onset (P &lt; .001). Our phylogenomic analyses revealed the emergence of two distinct genomic lineages of CP-CRKpn: ST45, harboring blaNDM, and ST1161, which carried blaKPC.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>AU and the frequency of CP-CRE increased after COVID-19 onset. The increase in CP-CRKpn was driven by the emergence of novel genomic lineages. Our observations highlight the need to strengthen infection prevention and control and antimicrobial stewardship efforts.</jats:p> </jats:sec>
30Scopus© Citations 36
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Validation of an NGS Panel Designed for Detection of Actionable Mutations in Tumors Common in Latin America
(2021)
Mauricio Salvo
;
Evelin González-Feliú
;
Jessica Toro
;
Iván Gallegos
;
Ignacio Maureira
<jats:p>Next-generation sequencing (NGS) is progressively being used in clinical practice. However, several barriers preclude using this technology for precision oncology in most Latin American countries. To overcome some of these barriers, we have designed a 25-gene panel that contains predictive biomarkers for most current and near-future available therapies in Chile and Latin America. Library preparation was optimized to account for low DNA integrity observed in formalin-fixed paraffin-embedded tissue. The workflow includes an automated bioinformatic pipeline that accounts for the underrepresentation of Latin Americans in genome databases. The panel detected small insertions, deletions, and single nucleotide variants down to allelic frequencies of 0.05 with high sensitivity, specificity, and reproducibility. The workflow was validated in 272 clinical samples from several solid tumor types, including gallbladder (GBC). More than 50 biomarkers were detected in these samples, mainly in BRCA1/2, KRAS, and PIK3CA genes. In GBC, biomarkers for PARP, EGFR, PIK3CA, mTOR, and Hedgehog signaling inhibitors were found. Thus, this small NGS panel is an accurate and sensitive method that may constitute a more cost-efficient alternative to multiple non-NGS assays and costly, large NGS panels. This kind of streamlined assay with automated bioinformatics analysis may facilitate the implementation of precision medicine in Latin America.</jats:p>
2Scopus© Citations 13
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A Novel Gemcitabine-Resistant Gallbladder Cancer Model Provides Insights into Molecular Changes Occurring during Acquired Resistance
(2023)
Luis Vergara-Gómez
;
Carolina Bizama
;
Jun Zhong
;
Kurt Buchegger
;
Felipe Suárez
<jats:p>Treatment options for advanced gallbladder cancer (GBC) are scarce and usually rely on cytotoxic chemotherapy, but the effectiveness of any regimen is limited and recurrence rates are high. Here, we investigated the molecular mechanisms of acquired resistance in GBC through the development and characterization of two gemcitabine-resistant GBC cell sublines (NOZ GemR and TGBC1 GemR). Morphological changes, cross-resistance, and migratory/invasive capabilities were evaluated. Then, microarray-based transcriptome profiling and quantitative SILAC-based phosphotyrosine proteomic analyses were performed to identify biological processes and signaling pathways dysregulated in gemcitabine-resistant GBC cells. The transcriptome profiling of parental and gemcitabine-resistant cells revealed the dysregulation of protein-coding genes that promote the enrichment of biological processes such as epithelial-to-mesenchymal transition and drug metabolism. On the other hand, the phosphoproteomics analysis of NOZ GemR identified aberrantly dysregulated signaling pathways in resistant cells as well as active kinases, such as ABL1, PDGFRA, and LYN, which could be novel therapeutic targets in GBC. Accordingly, NOZ GemR showed increased sensitivity toward the multikinase inhibitor dasatinib compared to parental cells. Our study describes transcriptome changes and altered signaling pathways occurring in gemcitabine-resistant GBC cells, which greatly expands our understanding of the underlying mechanisms of acquired drug resistance in GBC.</jats:p>
1Scopus© Citations 6
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Reduced microbial diversity of the nasopharyngeal microbiome in household contacts with latent tuberculosis infection
(2023)
Cinthya Ruiz-Tagle
;
Juan A. Ugalde
;
Rodrigo Naves
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ARAOS BRALIC, RAFAEL IGNACIO
;
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
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Real-World Performance of Susceptibility Testing for Ceftolozane/Tazobactam against Non-Carbapenemase-Producing Carbapenem-Resistant Pseudomonas aeruginosa
(2022)
RIVAS JIMENEZ, LINA MARIA
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Manuel Alcalde-Rico
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José R. W. Martínez
;
María Victoria Moreno
;
Pamela Rojas
<jats:p> Ceftolozane/tazbactam (C/T) is a potent anti-pseudomonal agent that has clinical utility against infections caused by non-carbapenemase, producing-carbapenem-resistant <jats:named-content content-type="genus-species">Pseudomonas aeruginosa</jats:named-content> (non-CP-CR-PA). Accurate, precise, and reliable antimicrobial susceptibility testing (AST) is crucial to guide clinical decisions. </jats:p>
19Scopus© Citations 2

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