Interactions between staphylococcal enterotoxins A and D and superantigen-like proteins 1 and 5 for predicting methicillin and multidrug resistance profiles among Staphylococcus aureus ocular isolates

Abstract

Background Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant (MDR) S. aureus strains are well recognized as posing substantial problems in treating ocular infections. S. aureus has a vast array of virulence factors, including superantigens and enterotoxins. Their interactions and ability to signal antibiotics resistance have not been explored. Objectives To predict the relationship between superantigens and methicillin and multidrug resistance among S. aureus ocular isolates. Methods We used a DNA microarray to characterize the enterotoxin and superantigen gene profiles of 98 S. aureus isolates collected from common ocular sources. The outcomes contained phenotypic and genotypic expressions of MRSA. We also included the MDR status as an outcome, categorized as resistance to three or more drugs, including oxacillin, penicillin, erythromycin, clindamycin, moxifloxacin, tetracycline, trimethoprim-sulfamethoxazole and gentamicin. We identified gene profiles that predicted each outcome through a classification analysis utilizing Random Forest machine learning techniques. Findings Our machine learning models predicted the outcomes accurately utilizing 67 enterotoxin and superantigen genes. Strong correlates predicting the genotypic expression of MRSA were enterotoxins A, D, J and R and superantigen-like proteins 1, 3, 7 and 10. Among these virulence factors, enterotoxin D and superantigen-like proteins 1, 5 and 10 were also significantly informative for predicting both MDR and MRSA in terms of phenotypic expression. Strong interactions were identified including enterotoxins A (entA) interacting with superantigen-like protein 1 (set6-var1_11), and enterotoxin D (entD) interacting with superantigen-like protein 5 (ssl05/set3_probe 1): MRSA and MDR S. aureus are associated with the presence of both entA and set6-var1_11, or both entD and ssl05/set3_probe 1, while the absence of these genes in pairs indicates non-multidrug-resistant and methicillin-susceptible S. aureus. Conclusions MRSA and MDR S. aureus show a different spectrum of ocular pathology than their non-resistant counterparts. When assessing the role of enterotoxins in predicting antibiotics resistance, it is critical to consider both main effects and interactions.

First study on diversity and antimicrobial-resistant profile of staphylococci in sports animals of Southern Thailand

“…Moreover, the coexistence rate of the mecA and blaZ genes in S. Sciuri was extremely high (> 90%) in this study, compared to a previous study [71], raising serious concern for AMR in this species because the mecA and blaZ genes coexist often in other staphylococci species, including S. pseudintermedius and S. aureus [72][73][74][75][76]. The majority of MRSS in this study also had an MDR phenotype which is rarely reported; MDR staphylococci are mainly S. aureus [77][78][79][80]. MRSS carrying multiple AMR genes might threaten animal and human health because this pathogen is capable of causing a variety of diseases and transmit AMR genes to other staphylococci [43][44][45][46][47][53][54][55].…”

Genomics of Staphylococcus aureus Strains Isolated from Infectious and Non-Infectious Ocular Conditions

“…S. aureus strains isolated from atopic patients experiencing keratoconjunctivitis with corneal ulceration, possessed enterotoxins more frequently compared to patients with no ulceration [ 56 ]; the role of enterotoxins in ocular infections remains to be fully defined. Another study found enterotoxin and enterotoxin-like genes were found to be highly correlated with MRSA and predictive for MDR status in ocular isolates [ 57 ]. The antibiotic susceptibility data of the isolates used in the current study shows that most of the strains were multi-drug resistant (MDR) [ 12 ], so the distribution of enterotoxin-like genes in 28% of MRSA USA infectious strains (MK + conjunctivitis) may indicate their MDR status, but the presence of enterotoxin-like genes in MSSA (methicillin sensitive S. aureus ) MDR strains from other conditions indicates enterotoxin genes are probably associated with the source of isolation.…”

Telehealth utilization in U.S. Medicare beneficiaries aged 65 years and older during the COVID-19 pandemic

“…A weighted chi-squared test was used for the descriptive overview of each predictor. Random Forest [ 40 ] model was applied for the multivariate classification analysis, which is a modern machine learning technique that has been utilized to select replicable sets of exploratory factors from a large number of predictors [ 42 – 47 ]. Because this method is completely nonparametric without any restrictive underlying model assumptions, nonlinear and complex interrelationships can be robustly accounted for.…”