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The emergence of methicillin-resistant Staphylococcus aureus (MRSA) several years ago highlighted the challenge of multidrug-resistant infections, emphasizing the critical need for innovative treatment approaches. Myrtenol, known for its antibacterial and antibiofilm properties, holds promise as a potential treatment option. This study aimed to evaluate the effectiveness of myrtenol against MRSA. The collected MRSA isolates were assessed for antimicrobial susceptibility following the Clinical and Laboratory Standards Institute (CLSI) guidelines 2023. Biofilm formation by MRSA was evaluated using the tissue culture plate (TCP) technique. The minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), and minimal biofilm inhibitory concentration (MBIC) of myrtenol against MRSA were determined both individually and in combination with antibiotics. Real-time PCR was employed to investigate the impact of myrtenol on the expression of virulence genes (sarA, agrA, and icaD) across the isolates. In this study, MRSA was identified in 90 out of 400 cases (22.5%) of hospital-acquired pathogens. Among the collected MRSA isolates, 53 out of 90 (59%) were found to produce biofilms. The MIC of myrtenol was comparable to the MBC across all tested isolates, they were almost the same. Combinations of myrtenol with most tested antibiotics exhibited synergistic effects exceeding 60%. Among the 53 biofilm-producing isolates, 45 isolates (85%) expressed the sarA gene, 49% expressed the agrA gene, and all biofilm-producing MRSA isolates (100%) expressed the icaD gene. A notable reduction in the relative quantity (RQ) values of virulence gene expression was observed after treatment with the MBIC of myrtenol across all tested isolates. Myrtenol demonstrated strong antimicrobial activity against MRSA, notably reducing the expression of key virulence genes linked to biofilm formation. This suggests its potential as a therapeutic agent for treating biofilm-associated MRSA infections.
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Introduction: The host genetic background is a crucial factor that underlies the interindividual variability of COVID-19 fatality and outcomes. Angiotensin-converting enzyme-2 (ACE-2) and interferon-induced transmembrane protein-3 (IFITM-3) have a key role in viral cell entrance and priming. The evoked immune response will also provide a predictive prognosis for COVID-19 infection. This study aimed to explore the association between ACE-2 and IFITM-3 genotypes and their corresponding allele frequencies with disease severity indices in the Egyptian COVID-19 population. The serum level of interleukin-6, as a biomarker of hyperinflammatory response, and cytokine storm, was correlated with disease progression, single nucleotide polymorphisms (SNPs) of the selected receptors, and treatment response. Methodology. We enrolled 900 COVID-19-confirmed cases and 100 healthy controls. Genomic DNA was extracted from 200 subjects (160 patients selected based on clinical and laboratory data and 40 healthy controls). The ACE-2 rs2285666 and IFITM-3 rs12252 SNPs were genotyped using the TaqMan probe allelic discrimination assay, and the serum IL-6 level was determined by ELISA. Logistic regression analysis was applied to analyze the association between ACE-2 and IFITM-3 genetic variants, IL-6 profile, and COVID-19 severity. Results: The identified genotypes and their alleles were significantly correlated with COVID-19 clinical deterioration as follows: ACE2 rs2285666 CT + TT, odds ratio (95% confidence interval): 12.136 (2.784-52.896) and IFITM-3 rs12252 AG + GG: 17.276 (3.673-81.249), both p < 0.001. Compared to the controls, the heterozygous and mutant genotypes for both SNPs were considerable risk factors for increased susceptibility to COVID-19. IL-6 levels were significantly correlated with disease progression (p < 0.001). Conclusion: ACE-2 and IFITM-3 genetic variants are potential predictors of COVID-19 severity, critical outcomes, and post-COVID-19 complications. Together, these SNPs and serum IL-6 levels explain a large proportion of the variability in the severity of COVID-19 infection and its consequences among Egyptian subjects.
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Background and Aims: Reports examine quinolone resistance mechanisms among Pseudomonas spp. are sporadic in the Kingdom of Saudi Arabia (KSA). We previously examined the genetic bases of plasmid-mediated quinolone resistance among Pseudomonas spp. clinical isolates. This study investigated chromosomally mediated quinolone resistance mechanisms via investigation of the mutations in the gyrA and parC genes. Methods: The minimum inhibitory concentration (MIC) to different quinolones was determined. Twenty-nine quinolone resistant Pseudomonas spp. clinical isolates were included. The gyrA and parC genes were sequenced by Sanger capillary electrophoresis. Multiple sequence alignment for the translated gyrA and parC genes was performed to identify mutation sites. Results: Of the 29 isolates, 27 isolates were P. aeruginosa and two were P. putida. The cluster analysis of the quinolone susceptibility pattern revealed seven susceptibility phenotypes (A-G) based on susceptibility patterns rather than the MIC values. Also, 22 different susceptibility phenotypes were detected based on MIC values. All isolates exhibited a missense mutation at position 83 (S83I/T/F) of the gyrA gene in addition to six missense mutations at positions outside the QRDR of this gene. In addition, 82.8% (24/29) of the isolates harbored a missense mutation in the parC gene at position 87 (S87L), along with six novel mutations outside the QRDR of the parC gene. Haplotyping of the gyrA, parC, and the overall QRDR revealed six, 10, and 13 different haplotypes, respectively. Conclusion: This study documents the incidence of the commonly reported mutations in the gyrA and parC genes in addition to novel mutations in these genes among Pseudomonas spp. clinical isolates recovered from KSA. Together with our previous findings, these data provide an insight into the genetic background of quinolone resistance among Pseudomonas spp. clinical isolates in KSA.