Altered competitive fitness, antimicrobial susceptibility, and cellular morphology in a triclosan-induced small-colony variant of staphylococcus aureus

Staphylococcus aureus can produce small-colony variants (SCVs) that express various phenotypes. While their significance is unclear, SCV propagation may be influenced by relative fitness, antimicrobial susceptibility, and the underlying mechanism. We have investigated triclosan-induced generation of SCVs in six S. aureus strains, including methicillin-resistant S. aureus (MRSA). Parent strains (P0) were repeatedly passaged on concentration gradients of triclosan using a solid-state exposure system to generate P10. P10 was subsequently passaged without triclosan to generate X10. Susceptibility to triclosan and 7 antibiotics was assessed at all stages. For S. aureus ATCC 6538, SCVs were further characterized by determining microbicide susceptibility and competitive fitness. Cellular morphology was examined using electron microscopy, and protein expression was evaluated through proteomics. Triclosan susceptibility in all SCVs (which could be generated from 4/6 strains) was markedly decreased, while antibiotic susceptibility was significantly increased in the majority of cases. An SCV of S. aureus ATCC 6538 exhibited significantly increased susceptibility to all tested microbicides. Cross-wall formation was impaired in this bacterium, while expression of FabI, a target of triclosan, and IsaA, a lytic transglycosylase involved in cell division, was increased. The P10 SCV was 49% less fit than P0. In summary, triclosan exposure of S. aureus produced SCVs in 4/6 test bacteria, with decreased triclosan susceptibility but with generally increased antibiotic susceptibility. An SCV derived from S. aureus ATCC 6538 showed reduced competitive fitness, potentially due to impaired cell division. In this SCV, increased FabI expression could account for reduced triclosan susceptibility, while IsaA may be upregulated in response to cell division defects

Fatty acid supplementation reverses the small colony variant phenotype in triclosan-adapted staphylococcus aureus: Genetic, proteomic and phenotypic analyses

Staphylococcus aureus can develop a small colony variant (SCV) phenotype in response to sub-lethal exposure to the biocide triclosan. In the current study, whole genome sequencing was performed and changes in virulence were investigated in five Staphylococcus aureus strains following repeated exposure to triclosan. Following exposure, 4/5 formed SCV and exhibited point mutations in the triclosan target gene fabI with 2/4 SCVs showing mutations in both fabI and fabD. The SCV phenotype was in all cases immediately reversed by nutritional supplementation with fatty acids or by repeated growth in the absence of triclosan, although fabI mutations persisted in 3/4 reverted SCVs. Virulence, determined using keratinocyte invasion and Galleria mellonella pathogenicity assays was significantly (p < 0.05) attenuated in 3/4 SCVs and in the non-SCV triclosan-adapted bacterium. Proteomic analysis revealed elevated FabI in 2/3 SCV and down-regulation in a protein associated with virulence in 1/3 SCV. In summary, attenuated keratinocyte invasion and larval virulence in triclosan-induced SCVs was associated with decreases in growth rate and virulence factor expression. Mutation occurred in fabI, which encodes the main triclosan target in all SCVs and the phenotype was reversed by fatty acid supplementation, demonstrating an association between fatty acid metabolism and triclosan-induced SCV

Enhanced Recovery After Surgery (ERAS) Protocols In General Surgery: A Review Of Implementation And Outcomes

ERAS is a group of protocols that aim at affecting positively patients &amp; surrounding lives. surgeons, nurses, physiotherapists, anesthetists, and even healthcare centers hospitals, labs, and pharmacies. Reducing the cost for both hospitals &amp;patients, decreasing the duration of residency in hospitals, and improving patient compliance, developing performance &amp; increasing teamwork between medical staff and patients all fall under the advantages of ERAS. Since it affects the 3 stages of any operation (preoperative-intraoperative-perioperative) it was necessary to implement a suitable protocol for each patient to achieve the best results mostly quitting smoking, fasting for a period before surgery, maintaining body temperature, pressure, and glucose level and the postoperative instructions , care &amp; nutrition to guarantee success and avoidance to recurrence or complications

Bacterial Coinfection and Antibiotic Resistance Profiles among Hospitalised COVID-19 Patients

While it is reported that COVID-19 patients are more prone to secondary bacterial infections, which are strongly linked to the severity of complications of the disease, bacterial coinfections associated with COVID-19 are not widely studied. This work aimed to investigate the prevalence of bacterial coinfections and associated antibiotic resistance profiles among hospitalised COVID-19 patients. Age, gender, weight, bacterial identities, and antibiotic sensitivity profiles were collected retrospectively for 108 patients admitted to the intensive care unit (ICU) and non-ICU ward of a single center in Saudi Arabia. ICU patients (60%) showed a significantly higher percentage of bacterial coinfections in sputum (74%) and blood (38%) samples, compared to non-ICU. Acinetobacter baumannii (56%) and Klebsiella pneumoniae (56%) were the most prevalent bacterial species from ICU patients, presenting with full resistance to all tested antibiotics except colistin. By contrast, samples of non-ICU patients exhibited infections with Escherichia coli (31%) and Pseudomonas aeruginosa (15%) predominantly, with elevated resistance of E. coli to piperacillin/tazobactam and trimethoprim/sulfamethoxazole. This alarming correlation between multi-drug resistant bacterial coinfection and admission to the ICU requires more attention and precaution with prescribed antibiotics to limit the spread of resistant bacteria and improve therapeutic management

Effectiveness of Oil-based Nanoemulsions with Molecular Docking of its Antimicrobial Potential

The biological properties of plant oils are improved by their conversion to nanoemulsions (NEs). This study evaluated the antimicrobial, antioxidant, and anti-hemolytic efficacy of coconut and salad rocket oils and their NEs. The result of the gas chromatography-mass spectroscopy analysis of the oils showed varied constituents such as palmitic acid, trimethylsilyl ester; 2,3-bis(acetyloxy)propyl laurate in salad rocket oil, 2-lauro-1,3-didecoin, n-butyl laurate; laurin, tri-; laurin in coconut oil. NEs diameter of salad rocket and coconut oils was 24.6 and 29.2 nm, respectively. More inhibitory activity of NEs compared with non-NEs form against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Salmonella typhi, Candida albicans, and Aspergillus flavus was detected. Coconut oil and its NEs caused 14.3% (anti-hemolysis 85.7%) and 22% hemolysis (anti-hemolysis 78%), respectively. Salad rocket oil and its NEs caused hemolysis 3.4% and 20.9%, respectively at 1000 µg/mL. Antioxidant activity of salad rocket and coconut oil reflected more IC50 (39.3 and 109.4 µg/mL) than its NEs (35.8 and 80.5 µg/mL), respectively. Molecular docking of trimethylsilyl ester and 2-lauro-1,3-didecoin against S. aureus (PDB=7BGE) and C. albicans protein (PDB=3DRA) revealed optimal binding mode that had the most energy interaction with the binding sites

Antibiogram of Urinary Tract Infections and Sepsis among Infants in Neonatal Intensive Care Unit

Neonatal infections including sepsis and urinary tract infections are considered among the leading causes of mortality in neonatal intensive care units (NICU). Thus, use of empiric antibiotics is very important in infected neonates and the success of this practice is mainly reliant on the availability of an up-to-date antibiogram for currently used antibiotic drugs. In this study, we aim to determine the bacteriological profile and antibiotic susceptibility pattern of bacteria isolated from blood or/and urine cultures belonging to patients at the NICU. A total of 54 urine samples were collected in the period between January 2015 and December 2019. Data of infants with positive urine and blood bacterial isolates were gathered retrospectively. The most commonly isolated bacteria from urine observed were K. pneumoniae (44%) and E. coli (39%), while Acinetobacter baumannii (33%) and K. pneumoniae (22%) predominated in neonatal blood samples. The majority of uropathogens and blood isolates exhibited low resistance to imipenem and tigecycline, respectively. These antibiotics would be recommended for future use as empirical treatment in neonates with urinary tract infections and/or sepsis. This investigation highlights the importance of surveillance studies to manage and ensure the effectiveness of treatment plan for critically ill infants

Antibiofilm, Antimicrobial, Anti-Quorum Sensing, and Antioxidant Activities of Saudi Sidr Honey: In Vitro and Molecular Docking Studies

Sidr honey is a valuable source of bioactive compounds with promising biological properties. In the present study, antimicrobial, antioxidant, and anti-quorum sensing properties of Saudi Sidr honey were assessed, along with phytochemical analysis, via gas chromatography–mass spectrometry (GC-MS). In silico study was also carried out to study the drug-likeness properties of the identified compounds and to study their affinity with known target proteins assessed using molecular docking approach. The results showed that Saudi Sidr honey exhibited promising antibacterial activity, with MIC values ranging from 50 to 400 mg/mL and MBC values from 50 to >450 mg/mL. Interestingly, the Saudi Sidr honey was active against Candida auris and Candida neoformans, with an MIC value of about 500 mg/mL. Moreover, the Sidr honey showed important antioxidant activities (ABTS assay: IC50 5.41 ± 0.045 mg/mL; DPPH assay: IC50 7.70 ± 0.065 mg/mL) and β-carotene bleaching test results (IC50 ≥ 20 mg/mL). In addition, the Saudi Sidr honey was able to inhibit biofilm formation on glass slides at 1/2 MIC by 77.11% for Bacillus subtilis, 70.88% for Staphylococcus aureus, 61.79% for Escherichia coli, and 56.64% for Pseudomonas aeruginosa. Similarly, violacein production by Chromobacterium violaceum was reduced by about 56.63%, while the production of pyocyanin by P. aeruginosa was decreased to 46.27% at a low concentration of Saudi Sidr honey. ADMET properties showed that five identified compounds, namely, 1-cyclohexylimidazolidin-2-one, 3-Butyl-3-methylcyclohexanone, 4-butyl-3-methoxy-2-cyclo penten-1-one, 2,2,3,3-Tetramethyl cyclopropane carboxylic acid, and 3,5-dihydroxy-2-(3-methylbut-2-en-1-yl showed promising drug-likeness properties. The compound 3,5-dihydroxy-2-(3-methylbut-2-en-1-yl exhibited the highest binding energy against antimicrobial and antioxidant target proteins (1JIJ, 2VAM, 6B8A, 6F86, 2CDU, and 1OG5). Overall, the obtained results highlighted the promising potential of Saudi Sidr honey as a rich source of bioactive compounds that can be used as food preservatives and antimicrobial, antioxidant, and anti-quorum sensing molecules

Phytochemical Characterization and Efficacy of <i>Artemisia judaica</i> Extract Loaded Chitosan Nanoparticles as Inhibitors of Cancer Proliferation and Microbial Growth

Despite the advanced development in the field of drug discovery and design, fighting infectious and non-infectious diseases remains a major worldwide heath challenge due to the limited activity of currently used drugs. Nevertheless, in recent years, the approach of designing nanoparticles for therapeutic applications has gained more interest and promise for future use. Thus, the current study is focused on the evaluation of A. judaica extract and chitosan nanoparticles loaded extract (CNPsLE) for potential antimicrobial and anticancer activities. The HPLC analysis of the extract has shown the presence of various phenolic and flavonoid compounds, including kaempferol (3916.34 µg/mL), apigenin (3794.32 µg/mL), chlorogenic acid (1089.58 µg/mL), quercetin (714.97 µg/mL), vanillin (691.55 µg/mL), naringenin (202.14 µg/mL), and rutin (55.64 µg/mL). The extract alone showed higher MIC values against B. subtilis, E. coli, S. aureus, K. pneumonia, and C. albicans (62.5, 15.65, 15.62, 31.25, and 31.25 µg/mL, respectively), whereas lower MIC values were observed when the extract was combined with CNPsLE (0.97, 1.95, 3.9, 4.1, and 15.62 µg/mL, respectively). The extract exhibited low cytotoxicity against normal Vero cells with IC50 173.74 µg/mL in comparison with the cytotoxicity of the CNPsLE (IC50, 73.89 µg/mL). However, CNPsLE showed more selective toxicity against the human prostate cancer cell line (PC3) with IC50 of 20.8 µg/mL than the extract alone with 76.09 µg/mL. In the docking experiments, kaempferol and apigenin were revealed to be suitable inhibitors for prostate cancer (2Q7L). Overall, the obtained data highlighted the promising potential therapeutic use of CNPsLE as an anticancer and antimicrobial agent

Current Insights into Diagnosis, Prevention Strategies, Treatment, Therapeutic Targets, and Challenges of Monkeypox (Mpox) Infections in Human Populations

In the wake of the emergence and worldwide respread of a viral infection called Monkeypox (Mpox), there is a serious threat to the health and safety of the global population. This viral infection was endemic to the western and central parts of Africa, but has recently spread out of this endemic area to various countries, including the United Kingdom (UK), Portugal, Spain, the United States of America (USA), Canada, Sweden, Belgium, Italy, Australia, Germany, France, the Netherlands, Israel, and Mexico. This is a timely review focusing on recent findings and developments in the epidemiology, clinical features, therapeutic targets, diagnosis, prevention mechanisms, research challenges and possible treatment for Mpox. To date (29 November 2022), there have been around 81,225 reported cases of Mpox. In most cases, this illness is mild; however, there is a fatality rate ranging from 1 to 10%, which might be increased due to associated complications and/or secondary infections. There is a real challenge in the diagnosis of Mpox, since its symptoms are very similar to those of other infections, including smallpox and chickenpox. Generally, to prevent/limit the risk and transmission of Mpox, the detection and isolation of infected individuals, as well as hand hygiene and cleanliness, are essential and effective approaches to control/combat this viral infection. Nevertheless, updated information about Mpox from different angles is lacking. Thus, this review provides updated and comprehensive information about the Mpox illness, which should highlight the global burden, pathogenicity, symptoms, diagnosis, prevention measures and possible treatment of this emerging disease