DIAZ ORTIZ, SANDRA LORENA
Preferred name
DIAZ ORTIZ, SANDRA LORENA
Main Affiliation
ORCID
0000-0002-9783-1956
Scopus Author ID
15135761400
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Item type:Product, Dataset - 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(United States National Library of Medicine, 2025); ; ; ;ROBERTO ANDRES RIQUELME NEIRA - Some of the metrics are blocked by yourconsent settings
Item type:Publication, P-310. Evolutionary dynamics of the Chilean-Cordobes MRSA clone allowed the emergence of new MRSA clones in Chile(Oxford University Press (OUP), 2025-01-29) ;MartĂnez, Jose R W ;Campbell, Amy; ; Background The global spread of methicillin-resistant Staphylococcus aureus (MRSA) is associated with distinct clones predominating in specific geographical regions. Available evidence suggests that the Chilean-Cordobes clone (ChC), an ST5-SCCmecI lineage, has predominated in Chilean hospitals ever since its first description in 1998. However, we recently reported a gradual decrease in this lineage over time, with frequencies dropping from 94% (2000) to 52% (2016). To understand this clonal replacement event, we aimed to reconstruct the genomic evolution of the ChC in Latin America. Characterization of clades and sub-lineages of the ChC clone.Figure 1.Characterization of clades and sub-lineages of the ChC clone. A) Maximum clade credibility molecular clock analysis of the 596 MRSA genomes. A Bayesian molecular clock analysis was performed with BEAST using the isolation date of each genome as calibrator. The vertical lines show the scale of years. The colored strip showed the country of origin. The dots show the presence of mecA genotypes, heavy metal resistance genes (HMRGs), and SNPs in Sau1. The branches are colored based on the sub-lineage identification: ChC-I (magenta), ChC-II (orange), and ChC-III (green). B) Characterization of the ChC clades. The presence of each genetic element considered to characterize the clades are marked by a + symbol. C) Relative frequency of the ChC sub-lineages in Chile over time. The colored bars represent the relative frequency of each sub-lineage: ChC-I (magenta), ChC-II (orange), ChC-III (green), and unclassified (gray). Methods A total of 596 ChC MRSA isolates obtained from 6 Latin American countries between 1999-2018 were whole-genome sequenced and characterized using a Bayesian molecular clock analysis (MCA). Sub-lineages (SLs) observed in major divergence events were further characterized. Additionally, the frequency of each SL observed in our 1999-2018 collection was assessed in an independent group of genomes from 274 Chilean clinical MRSA isolates collected in 2022. Results Our MCA of ChC MRSA revealed 3 clades strongly related with different genomic traits, including: i) mecA genotype, ii) heavy metal resistance genes (HMRGs), and iii) changes in the Sau1 restriction-modification system (Sau1) (Fig. 1A). Each clade was classified as sub-lineage: ChC-I, ChC-II, and ChC-III (Fig. 1B). All the genomes from Argentina, Colombia, and Venezuela – countries where ChC was largely replaced - belonged to the ChC-II SL and harbored a Sau1 mutation (Fig. 1A). On the other hand, genomes obtained from Chile distributed in different SLs and exhibited a dynamic interchange over time (Fig. 1C). While between 1999-2003 most of the genomes belonged to SLs ChC-I and ChC-II, both SLs virtually disappeared in 2013-2018, period were >90% ChC genomes corresponded to ChC-III (Fig. 1C). In 2022, a majority of ChC MRSA had genomic features compatible with the ChC-III SL (Fig. 1C). Finally, the MCA revealed an evolutionary event within ChC-III dated in 2005, which was accompanied by the loss of HMRGs (Fig. 1A) Conclusion We describe the time evolution of several ChC clades, giving rise to sub-lineages that seem to play a role in the loss of dominance of the ChC MRSA clone in Chile and a consequent change in its epidemiology in the country. Disclosures JosĂ© M Munita, MD, MSD: Grant/Research Support|Pfizer: Grant/Research Support - Some of the metrics are blocked by yourconsent settings
Item type:Product, 11 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Dynamics of the MRSA Population in a Chilean Hospital: a Phylogenomic Analysis (2000–2016)(2023) ;JosĂ© R. W. MartĂnez ;Paul J. Planet ;Maria Spencer-Sandino; 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>4Scopus© Citations 12 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, 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. MartĂnez ;Manuel Alcalde-Rico ;EstefanĂa Jara-Videla ;Jinnethe ReyesLina 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 ConcepciĂłn). 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 ConcepciĂłn (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 ConcepciĂłn 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.4Scopus© Citations 2 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Actividad in vitro de ceftazidima/avibactam contra aislados clĂnicos de Klebsiella pneumoniae resistente a carbapenĂ©micos y comparaciĂłn de tĂ©cnicas de susceptibilidad(SciELO Agencia Nacional de Investigacion y Desarrollo (ANID), 2025-06) ;Valeria Quiroz; ;Katherine Soto ;Yohanna AntolĂnezValentina Sanfurgo7 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Multiomics characterization of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America(2022) ;Betsy E Castro ;Rafael Rios ;Lina P Carvajal ;Mónica L VargasMónica 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>1 3Scopus© 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. MartĂnez; 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 harboring15Scopus© Citations 11 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Membrane Lipids Augment Cell Envelope Stress Signaling via the MadRS System to Defend Against Antimicrobial Peptides and Antibiotics in <i>Enterococcus faecalis</i>(2025) ;William R Miller ;April Nguyen ;Kavindra V Singh ;Samie RizviAyesha KhanEnterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized 3-gene operon (madEFG) that protects the Enterococcus faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of a functional LiaFSR system and leads to persistence of cardiac microlesions in vivo. Moreover, changes in the lipid cell membrane environment alter CAMP susceptibility and expression of the MadRS system. Thus, we provide a framework supporting a multilayered envelope defense mechanism for resistance and survival coupled to virulence.Scopus© Citations 2 3 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Clinical characteristics, microbiology and outcomes of a cohort of patients treated with ceftolozane/tazobactam in acute care inpatient facilities, Houston, Texas, USA(2022) ;Truc T Tran ;Nicolo L Cabrera ;Anne J Gonzales-Luna ;Travis J CarlsonFaris Alnezary<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16–0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa.</jats:p> </jats:sec>2Scopus© Citations 6