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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.
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Clinical Outcomes and Bacterial Characteristics of Carbapenem-resistant <i>Acinetobacter Baumannii</i> Among Patients From Different Global Regions
(2023)
Minggui Wang
;
Lizhao Ge
;
Liang Chen
;
Lauren Komarow
;
Blake Hanson
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality.</jats:p> <jats:p>Clinical Trials Registration. NCT03646227.</jats:p> </jats:sec>
3Scopus© Citations 102
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Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort study
(2022)
Minggui Wang
;
Michelle Earley
;
Liang Chen
;
Blake M Hanson
;
Yunsong Yu
Scopus© Citations 226 7
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Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries
(2022)
María F. Mojica
;
Elsa De La Cadena
;
Rafael Ríos
;
Juan Carlos García-Betancur
;
Lorena Díaz
<jats:sec><jats:title>Objectives</jats:title><jats:p>Identify molecular mechanisms responsible for the <jats:italic>in vitro</jats:italic> non-susceptibility to ceftolozane/tazobactam (TOL) in a group of 158 clinical isolates of <jats:italic>Pseudomonas aeruginosa</jats:italic> from five Latin American countries collected before the introduction of TOL into the clinical practice.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Clinical isolates of <jats:italic>P. aeruginosa</jats:italic> (<jats:italic>n</jats:italic> = 504) were collected between January 2016 and October 2017 from 20 hospitals located in Argentina, Brazil, Chile, Colombia, and Mexico. Minimum inhibitory concentrations (MICs) to TOL were determined by standard broth microdilution and interpreted according to CLSI breakpoints. Initially, production of carbapenemases in TOL non-susceptible isolates was assessed by Rapidec® followed by qPCR to detect <jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>, <jats:italic>bla</jats:italic><jats:sub>NDM-1</jats:sub>, <jats:italic>bla</jats:italic><jats:sub>VIM</jats:sub>, and <jats:italic>bla</jats:italic><jats:sub>IMP</jats:sub>. Illumina® WGS was performed for isolates in which non-susceptibility to TOL was not mediated by carbapenemases.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 158 (31.3%) isolates were non-susceptible to TOL. In 74 (46.8%) of these isolates, non-susceptibility to TOL was explained by the production of at least one carbapenemase. WGS revealed that some isolates carried ESBLs, mutated <jats:italic>bla</jats:italic><jats:sub>PDC</jats:sub> and <jats:italic>ampD</jats:italic>, associated with decreased susceptibility to TOL.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Substitutions found in PDC and carbapenemase production were the most common presumed mechanisms of resistance to TOL detected in this study. This study shows that epidemiological surveillance is warranted to monitor the emergence of novel mechanisms of resistance to TOL that might compromise its clinical utility.</jats:p></jats:sec>
5Scopus© Citations 14
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Detection of heterogeneous vancomycin intermediate resistance in MRSA isolates from Latin America
(2020)
Betsy E Castro
;
Maritza Berrio
;
Monica L Vargas
;
Lina P Carvajal
;
Lina V Millan
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Vancomycin is a common first-line option for MRSA infections. The heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) phenotype is associated with therapeutic failure. However, hVISA isolates are usually reported as vancomycin susceptible by routine susceptibility testing procedures.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>To detect and characterize the hVISA phenotype in MRSA isolates causing infections in nine Latin American countries.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We evaluated a total of 1189 vancomycin-susceptible MRSA isolates recovered during 2006–08 and 2011–14. After an initial screening of hVISA using glycopeptide-supplemented agar strategies, the detection of hVISA was performed by Etest (GRD) and Macro-method (MET). Isolates deemed to be hVISA were subjected to population analysis profile/AUC (PAP/AUC) and WGS for further characterization. Finally, we interrogated alterations in predicted proteins associated with the development of the VISA phenotype in both hVISA and vancomycin-susceptible S. aureus (VSSA) genomes.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 39 MRSA isolates (3.3%) were classified as hVISA (1.4% and 5.6% in MRSA recovered from 2006–08 and 2011–14, respectively). Most of the hVISA strains (95%) belonged to clonal complex (CC) 5. Only 6/39 hVISA isolates were categorized as hVISA by PAP/AUC, with 6 other isolates close (0.87–0.89) to the cut-off (0.9). The majority of the 39 hVISA isolates exhibited the Leu-14→Ile (90%) and VraT Glu-156→Gly (90%) amino acid substitutions in WalK. Additionally, we identified 10 substitutions present only in hVISA isolates, involving WalK, VraS, RpoB and RpoC proteins.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The hVISA phenotype exhibits low frequency in Latin America. Amino acid substitutions in proteins involved in cell envelope homeostasis and RNA synthesis were commonly identified. Our results suggest that Etest-based methods are an important alternative for the detection of hVISA clinical isolates.</jats:p></jats:sec>
3 1Scopus© Citations 14

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