Molecular epidemiology of the Chilean-Cordobes clone in South America and the contribution of heavy metal resistance in the ability of MRSA to disseminate and prevail

Project Title

Partner Organisations

Facultad de Medicina Clínica Alemana Universidad del Desarrollo

Internal ID

1171805

Principal Investigator

MUNITA SEPULVEDA, JOSE MANUEL

Type

basic research

Status

TERMINADO

Start Date

2017

Investigators

Juan Ugalde

Publications

Now showing 1 - 10 of 13

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Managing All the Genotypic Knowledge: Approach to a Septic Patient Colonized by Different Enterobacteriales with Unique Carbapenemases
(2019)
Stacy C. Park
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Alexander M. Wailan
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Katie E. Barry
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Kasi Vegesana
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Joanne Carroll
<jats:p> The recent development of new antimicrobials active against carbapenemase-producing <jats:italic>Enterobacteriales</jats:italic> (CPE) has brought new hope for the treatment of infections due to these organisms. However, the evolving epidemiology of bacteria with carbapenemases may complicate management, as providers are faced with treating patients colonized by bacteria producing multiple carbapenemases. </jats:p>
Scopus© Citations 7 1
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Novel Strategies for the Management of Vancomycin-Resistant Enterococcal Infections
(2019)
German A. Contreras
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MUNITA SEPULVEDA, JOSE MANUEL
;
Cesar A. Arias
1Scopus© Citations 36
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Correction for Khan et al., “A Multicenter Study To Evaluate Ceftaroline Breakpoints: Performance in an Area with High Prevalence of Methicillin-Resistant Staphylococcus aureus Sequence Type 5 Lineage”
(2021)
Ayesha Khan
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Lina M. Rivas
;
Maria Spencer
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Rodrigo Martinez
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Marusella Lam
1 1
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Multiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America
(2022)
Betsy E Castro
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Rafael Rios
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Lina P Carvajal
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Mónica L Vargas
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Mónica P Cala
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) compromise the clinical efficacy of vancomycin. The hVISA isolates spontaneously produce vancomycin-intermediate Staphylococcus aureus (VISA) cells generated by diverse and intriguing mechanisms.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective</jats:title> <jats:p>To characterize the biomolecular profile of clinical hVISA applying genomic, transcriptomic and metabolomic approaches.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>39 hVISA and 305 VSSA and their genomes were included. Core genome-based Bayesian phylogenetic reconstructions were built and alterations in predicted proteins in VISA/hVISA were interrogated. Linear discriminant analysis and a Genome-Wide Association Study were performed. Differentially expressed genes were identified in hVISA-VSSA by RNA-sequencing. The undirected profiles of metabolites were determined by liquid chromatography and hydrophilic interaction in six CC5-MRSA.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Genomic relatedness of MRSA associated to hVISA phenotype was not detected. The change Try38 → His in Atl (autolysin) was identified in 92% of the hVISA. We identified SNPs and k-mers associated to hVISA in 11 coding regions with predicted functions in virulence, transport systems, carbohydrate metabolism and tRNA synthesis. Further, capABCDE, sdrD, esaA, esaD, essA and ssaA genes were overexpressed in hVISA, while lacABCDEFG genes were downregulated. Additionally, valine, threonine, leucine tyrosine, FAD and NADH were more abundant in VSSA, while arginine, glycine and betaine were more abundant in hVISA. Finally, we observed altered metabolic pathways in hVISA, including purine and pyrimidine pathway, CoA biosynthesis, amino acid metabolism and aminoacyl tRNA biosynthesis.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our results show that the mechanism of hVISA involves major changes in regulatory systems, expression of virulence factors and reduction in glycolysis via TCA cycle. This work contributes to the understanding of the development of this complex resistance mechanism in regional strains.</jats:p> </jats:sec>
1Scopus© Citations 8 3
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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
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Manuel Alcalde-Rico
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Estefanía Jara-Videla
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Jinnethe Reyes
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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.
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Corrigendum to “In Vivo Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa Arising by AmpC- and Non-AmpC-Mediated Pathways”
(2019)
Erik Skoglund
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Henrietta Abodakpi
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Rafael Rios
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Lorena Diaz
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Elsa De La Cadena
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Covid-19 in South America: clinical and epidemiological characteristics among 381 patients during the early phase of the pandemic in Santiago, Chile
(2020)
Macarena R. Vial
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Anne Peters
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Inia Pérez
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María Spencer-Sandino
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Mario Barbé
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Understanding the characteristics of the Covid-19 pandemic in different geographical regions, ethnic and socioeconomic settings are of emerging importance. This study presents the demographic and clinical features of SARS-CoV-2 infected patients in a large private healthcare center in Santiago, Chile, during the first month of the pandemic.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We analyzed the demographics, laboratory and clinical characteristics including severity and outcome of all patients diagnosed with Covid-19 during the first month of the pandemic. SARS-2-CoV infection was confirmed by RT-PCR in nosopharyngeal samples. The primary outcome was a composite of ICU admission or all-cause, in-hospital mortality. Clinical and laboratory parameters of hospitalized patients were analyzed regarding their association with the primary outcome.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>From March 3 to April 4, 2020, 3679 individuals were tested for SARS-CoV-2 in our hospital. Of those, 381 had Covid-19 and were included into this analysis. Most patients (99.2%) were Chileans, 12% returning from recent travel. The median age was 39 years (IQR 31–49) and 52% were female. A total of 88 patients (23.1%) were hospitalized; 18 (3.7%) required ICU and/or died. The overall mortality was 0.7%. Increased body mass index (BMI) and elevated C-reactive protein (CRP) were independently associated with ICU care or death.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>During the first weeks of the pandemic in Chile, most Covid-19 patients were young, with low rates of hospitalization, ICU requirement, and fatality. BMI and CRP on admission were predictors for severity. Our data provide important information on the clinical course and outcome of Covid-19 in a Latin American setting.</jats:p> </jats:sec>
1Scopus© Citations 15 3
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ESBL-Producing Escherichia coli Carrying CTX-M Genes Circulating among Livestock, Dogs, and Wild Mammals in Small-Scale Farms of Central Chile
(2021)
Julio A. Benavides
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Marília Salgado-Caxito
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Andrés Opazo-Capurro
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Paulina González Muñoz
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Ana Piñeiro
Antibiotic-resistant bacteria of critical importance for global health such as extended-spectrum beta-lactamases-producing (ESBL)-Escherichia coli have been detected in livestock, dogs, and wildlife worldwide. However, the dynamics of ESBL-E. coli between these animals remains poorly understood, particularly in small-scale farms of low and middle-income countries where contact between species can be frequent. We compared the prevalence of fecal carriage of ESBL-E. coli among 332 livestock (207 cows, 15 pigs, 60 horses, 40 sheep, 6 goats, 4 chickens), 82 dogs, and wildlife including 131 European rabbits, 30 rodents, and 12 Andean foxes sharing territory in peri-urban localities of central Chile. The prevalence was lower in livestock (3.0%) and wildlife (0.5%) compared to dogs (24%). Among 47 ESBL-E. coli isolates recovered, CTX-M-group 1 was the main ESBL genotype identified, followed by CTX-M-groups 2, 9, 8, and 25. ERIC-PCR showed no cluster of E. coli clones by either host species nor locality. To our knowledge, this is the first report of ESBL-E. coli among sheep, cattle, dogs, and rodents of Chile, confirming their fecal carriage among domestic and wild animals in small-scale farms. The high prevalence of ESBL-E. coli in dogs encourages further investigation on their role as potential reservoirs of this bacteria in agricultural settings.
Scopus© Citations 54 3
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Longitudinal assessment of SARS-CoV-2 IgG seroconversionamong front-line healthcare workers during the first wave of the Covid-19 pandemic at a tertiary-care hospital in Chile
(2021)
IRURETAGOYENA BRUCE, MIRENTXU INES
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Macarena R. Vial
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Maria Spencer-Sandino
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Pablo Gaete
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Anne Peters
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Healthcare workers (HCWs) are at high risk of exposure to SARS-CoV-2. Cross-sectional studies have provided variable rates of seroprevalence in HCWs. Longitudinal assessments of the serological response to Covid-19 among HCWs are crucial to understanding the risk of infection and changes in antibody titers over time. We aimed to investigate seroprevalence and risk factors associated with seroconversion in a prospective cohort of HCWs during the peak of the first wave of the Covid-19 pandemic.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We conducted a longitudinal study among 446 front-line HCWsin a tertiary-care hospital in Chile from April to July 2020. IgG was determined monthly using two different ELISAs in serum samples of HCWs, during the three-month period. In each visit, demographic data, symptoms, risk factors, and exposure risks were also assessed.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>The overall seroprevalence at the end of the study period was 24% (95% CI20.2–28.3), with 43% of seropositive HCWs reporting no prior symptoms. Seroconversion rates significantly differed over the study period, from 2.1% to as high as 8.8% at the peak of the epidemic. There were no statistically significant differences observed between HCWs in direct clinical care of patients with Covid-19 and those working in low risk areas. Antibody titers appeared to wane over time.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>HCWs were severely affected with a high rate of seroconversion that appeared to mirror the local epidemiological situation. A significant amount of participants underwent an asymptomatic infection, highlighting the need for improved surveillance policies. Antibody titers appear to wane over time; further studies to understand this finding’s impact on the risk of reinfection are warranted.</jats:p> </jats:sec>
1Scopus© Citations 21 2
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A One Health - One World initiative to control antibiotic resistance: A Chile - Sweden collaboration
(2019)
Jaime R. Cabrera-Pardo
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Rolf Lood
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Klas Udekwu
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Gerardo Gonzalez-Rocha
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MUNITA SEPULVEDA, JOSE MANUEL
Scopus© Citations 20 1

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