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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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      1Scopus© Citations 4
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    Scopus© Citations 4  2
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    Scopus© Citations 13  2
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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>
    Scopus© Citations 2  1
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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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    Real-World Performance of Susceptibility Testing for Ceftolozane/Tazobactam against Non-Carbapenemase-Producing Carbapenem-Resistant Pseudomonas aeruginosa
    (2022)
    RIVAS JIMENEZ, LINA MARIA  
    ;
    Manuel Alcalde-Rico
    ;
    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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    New Perspectives on Antimicrobial Agents: Long-Acting Lipoglycopeptides
    (2022)
    Truc T. Tran
    ;
    Sara Gomez Villegas
    ;
    Samuel L. Aitken
    ;
    Susan M. Butler-Wu
    ;
    Alex Soriano
    <jats:p>The long-acting lipoglycopeptides (LGPs) dalbavancin and oritavancin are semisynthetic antimicrobials with broad and potent activity against Gram-positive bacterial pathogens. While they are approved by the Food and Drug Administration for acute bacterial skin and soft tissue infections, their pharmacological properties suggest a potential role of these agents for the treatment of deep-seated and severe infections, such as bloodstream and bone and joint infections.</jats:p>
      5Scopus© Citations 29
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    A Multicenter Study To Evaluate Ceftaroline Breakpoints: Performance in an Area with High Prevalence of Methicillin-Resistant Staphylococcus aureus Sequence Type 5 Lineage
    (2019)
    Ayesha Khan
    ;
    Lina M. Rivas
    ;
    Maria Spencer
    ;
    Rodrigo Martinez
    ;
    Marusella Lam
    <jats:p> Ceftaroline (CPT) is a broad-spectrum agent with potent activity against methicillin-resistant <jats:named-content content-type="genus-species">Staphylococcus aureus</jats:named-content> (MRSA). The sequence type 5 (ST5) Chilean-Cordobés clone, associated with CPT nonsusceptibility, is dominant in Chile, a region with high rates of MRSA infections. </jats:p>
      1Scopus© Citations 7  1