Correction: Elwakil et al. Memory Impairment, Pro-Inflammatory Host Response and Brain Histopathologic Severity in Rats Infected with K. pneumoniae or P. aeruginosa Meningitis. Pathogens 2022, 11, 933.

In the original publication [...].

Whole Exome Sequence Analysis for Inborn Errors of IL-12/IFN-γ Axis in Patient with Recurrent Typhoid Fever.

Background: The IL-12/IFN-γ axis pathways play a vital role in the control of intracellular pathogens such as Salmonella typhi. Objective: The study is aimed at using whole exome sequencing (WES) to screen out genetic defects in IL-12/IFN-γ axis in patients with recurrent typhoid fever. Methods: WES using next-generation sequencing was performed on a single patient diagnosed with recurrent typhoid fever. Following alignment and variant calling, exomes were screened for mutations in 25 genes that are involved in the IL-12/IFN-γ axis pathway. Each variant was assessed by using various bioinformatics mutational analysis tools such as SIFT, Polyphen2, LRT, MutationTaster, and MutationAssessor. Results: Out of 25 possible variations in the IL-12/IFN-γ axis genes, only 2 probable disease-causing mutations were identified. These variations were rare and include mutations in IL23R and ZNFX I. Other pathogenic mutations were found, but they were not considered likely to cause disease based on various mutation predictors. Conclusion: Applying WES to the patient with recurrent typhoid fever detects variants that are not much important as other genes in the IL-12/IFN-γ axis. Results of the current study suggest that a large population sizes would be needed to examine the functional relevance of IL-12/IFN-γ axis genes with recurrent typhoid fever.

Memory Impairment, Pro-Inflammatory Host Response and Brain Histopathologic Severity in Rats Infected with K. pneumoniae or P. aeruginosa Meningitis.

Meningitis caused by Klebsiella pneumoniae and Pseudomonas aeruginosa has lately become a prevalent cause of the central nervous system (CNS) infection. Bacterial invasion into the subarachnoid space prompts the releasing mechanism of chemokines and pro-inflammatory cytokines. The present study aimed to compare K. pneumoniae and P. aeruginosa meningitis concerning the memory, pro-inflammatory mediators and brain histopathological changes at different time intervals in adult Albino rats. The animals were sacrificed at three time intervals comprising 5, 10 and 15 days after meningitis induction. Cerebrospinal fluid (CSF) culture, relative brain weights, complete blood analysis, biochemical markers, levels of cytokine, chemokine and brain-derived neurotrophic factor (BDNF), neurotransmitter acetylcholine esterase (AChE) activity, and the brain histopathology of the infected rats in comparison to those in the control group were assessed. There was a significant increase in the levels of pro-inflammatory cytokines and chemokines including TNF-α, IL-1ß, IL-6 and AChE after 5 days of bacterial meningitis infection with both K. pneumoniae and P. aeruginosa. The histopathological analysis of the cerebral cortex in the P. aeruginosa meningitis model at different time intervals revealed abundant numbers of dilated and congested blood vessels with severe hemorrhage, cerebral infarct, intracellular and extracellular vacuoles, and gliosis. Fifteen days post infection, a significant reduction in the brain tissue weight was observed. The meningitis model employing P. aeruginosa exhibited more evident time-dependent severity compared to K. pneumoniae, which may advocate its validity as a simple and effective research model to study meningitis of the CNS. This model may be utilized for further investigation to ascertain the molecular and biological association between bacterial meningitis and the development of the pathophysiological hallmarks underlying Alzheimer's disease in preclinical and clinical setups. Clinical extrapolation based on studies employing animal disease models should be carefully interpreted.

Antimicrobial Resistance and Its Spread Is a Global Threat.

Antimicrobial resistance (AMR) is a challenge to human wellbeing the world over and is one of the more serious public health concerns. AMR has the potential to emerge as a serious healthcare threat if left unchecked, and could put into motion another pandemic. This establishes the need for the establishment of global health solutions around AMR, taking into account microdata from different parts of the world. The positive influences in this regard could be establishing conducive social norms, charting individual and group behavior practices that favor global human health, and lastly, increasing collective awareness around the need for such action. Apart from being an emerging threat in the clinical space, AMR also increases treatment complexity, posing a real challenge to the existing guidelines around the management of antibiotic resistance. The attribute of resistance development has been linked to many genetic elements, some of which have complex transmission pathways between microbes. Beyond this, new mechanisms underlying the development of AMR are being discovered, making this field an important aspect of medical microbiology. Apart from the genetic aspects of AMR, other practices, including misdiagnosis, exposure to broad-spectrum antibiotics, and lack of rapid diagnosis, add to the creation of resistance. However, upgrades and innovations in DNA sequencing technologies with bioinformatics have revolutionized the diagnostic industry, aiding the real-time detection of causes of AMR and its elements, which are important to delineating control and prevention approaches to fight the threat.

Antioxidant and Antimicrobial Potencies of Chemically-Profiled Essential Oil from Asteriscus graveolens against Clinically-Important Pathogenic Microbial Strains.

Recently, the antimicrobial potential of essential oils extracted from plants has gained extensive research interest, primarily for the development of novel antimicrobial treatments to combat emerging microbial resistance. The current study aims at investigating the antimicrobial activity and chemical composition of essential oil derived from gold coin daisy, which is known as Asteriscus graveolens (EOAG). In this context, a gas chromatography-tandem mass spectrometry (GC-MS) analysis of EOAG was conducted to identify its phytoconstituents. The in vitro antioxidant capacity of EOAG was determined by the use of three tests, namely: 1,1-diphenyl-2-picrylhydrzyl (DPPH), ferric reducing activity power (FRAP), and total antioxidant capacity (TAC). The antimicrobial activity of EOAG against clinically important bacterial (Escherichia coli, K12; Staphylococcus aureus, ATCC 6633; Bacillus subtilis, DSM 6333; and Pseudomonas aeruginosa, CIP A22) and fungal (Candida albicans, ATCC 10231; Aspergillus niger, MTCC 282; Aspergillus flavus, MTCC 9606; and Fusarium oxysporum, MTCC 9913) strains was assessed. Antimicrobial efficacy was determined on solid (inhibition diameter) and liquid media to calculate the minimum inhibitory concentration (MIC). GC/MS profiling of EOAG revealed that 18 compounds were identified, with a dominance of α-Thujone (17.92%) followed by carvacrol (14.14%), with a total identification of about 99. 92%. The antioxidant activity of EOAG was determined to have IC50 values of 34.81 ± 1.12 µg/mL (DPPH), 89.37 ± 5.02 µg/mL (FRAP), and 1048.38 ± 10.23 µg EAA/mg (TAC). The antibacterial activity in a solid medium revealed that the largest diameter was recorded in P. aeruginosa (28.47 ± 1.44 mm) followed by S. aureus (27.41 ± 1.54 mm), and the MIC in S. aureus was 12.18 ± 0.98 µg / mL. For the antifungal activity of EOAG, the largest inhibition diameter was found in F. oxysporum (33.62 ± 2.14 mm) followed by C. albicans (26.41 ± 1.90 mm), and the smallest MIC was found in F. oxysporum (18.29 ± 1.21 µg/mL) followed by C. albicans (19.39 ± 1.0 µg/mL). In conclusion, EOAG can be useful as a natural antimicrobial and antioxidant agent and an alternative to synthetic antibiotics. Hence, they might be utilized to treat a variety of infectious disorders caused by pathogenic microorganisms, particularly those that have gained resistance to standard antibiotics.

Antibiotic sensitivity of Mycobacterium tuberculosis isolates; a retrospective study from a Saudi tertiary hospital.

OBJECTIVES: This study aims to examine the antibiotic sensitivity of Mycobacterium tuberculosis isolates and its drug resistance. We also evaluated the relationship between demographic characteristics and tuberculosis (TB) drug susceptibilities. METHODS: A retrospective study was conducted to analyse the antibiotic sensitivity of M. tuberculosis isolates and its resistance to first-line anti-TB drugs. During the period 2008-2013, the medical records of 191 patients from the TB ward and the Out-Patient Department in an Eastern KSA tertiary hospital were reviewed. RESULTS: We classified the specimens into two categories: extra-pulmonary and pulmonary TB. Among the extra-pulmonary TB specimens, 36.5% were from body fluids, 29.2% from tissue cultures and 5.2% from body abscesses. In case of pulmonary TB, sputum samples accounted for the highest proportion of the specimens (28.6%), followed by bronchial aspirates and pleural fluid (13.2% and 5.7%, respectively). Clinical isolates from women showed higher resistance to ethambutol compared to those from men. Isoniazid showed the highest resistance pattern among all antibiotics tested (17%). Meanwhile, tissue cultures had higher resistance to Isoniazid antibiotic compared to the other specimens. CONCLUSION: Resistance to first-line TB drugs is higher in extra-pulmonary TB isolates than pulmonary isolates. Nearly one-fourth of all M. tuberculosis clinical strains were resistant to the antibiotics tested in mono-resistant or multi-resistant manners. Women had greater resistance to TB drug ethambutol as compared to men. Meanwhile, extra-pulmonary TB specimens, specifically that from tissue cultures, showed greater resistance to Isoniazid than other clinical specimens.

Influenza vaccine acceptance by healthcare workers in Saudi Arabia: A questionnaire-based analysis.

The aim of this study was to gauge the reasons for accepting or declining influenza vaccine in healthcare staff in Saudi Arabia. A questionnaire was administered to healthcare workers in Saudi Arabia. In all, 633 respondents who provided gender, nationality and profession were included. Reasons for vaccine uptake or refusal were assessed according to profession and educational level. Uptake of vaccine was lower in the period from 2010 to 2014 (3-13.3%) compared to pre-2010 figures (20.7%), rising to 44.1% in 2015. Comparing data for 'never having been vaccinated' to 'being vaccinated in 2015', there was no significant difference in distribution between nurses (9.27% v 38.8%), physicians (13.9% v 56.0%) and laboratory technicians (15.9% v 33.5%) (p= 0.08). The top reason for vaccination was protection of self and family, while the top reason for refusal was not considering the vaccine to be necessary. Education level had no significant effect on the likelihood of being vaccinated. Improvement of healthcare worker vaccination levels in Saudi Arabia might be achieved by addressing staff concerns on vaccine safety and efficacy, emphasizing the potential dangers of influenza and capitalizing on the staff's focus on protecting themselves and their families.

Role of bacterial Ser/Thr protein kinases spr 1577 in the pathogenesis of respiratory infections caused by S. pneumoniae.

This study investigated the specific role played by conserved membrane eukaryotic-like Ser/Thr protein kinases (StkP) during infection, particularly pneumonia, in order to get deep insights about Ser/Thr protein kinases signaling during infection and pathogenesis. The wild type and mutated Ser/Thr protein kinases (Spr1577) strains were tested on different cell lines to understand their virulence based on gentamicin protection assay, gene expression analysis and the expression of various interleukins. Though there was no uptake of bacterial CFU at the beginning, after 24 h it was 50% less for the mutated in comparison to wild-type strain, thus indicating a possible role of Spr1577 gene in the phagosomal survival of S pneumoniae. The complemented, strain-restored bacterial survival to the similar extent alike wild-type strains suggest that the Spr1577 kinase activity is not critical for the intracellular survival of S. pneumoniae within macrophages. Peak expression of spr1577 post infection indicating that the virulent genes seemed persuaded within the macrophages. Higher induction of pro-inflammatory cytokines by the wild type and complemented strains, but not by mutated strain, suggest its role in the induction of macrophages functions. S. pneumoniae and S. pyogenes are closely-related pathogens having 97% similarity in their gene sequences suggesting that the virulence mechanisms greatly varies and remain poorly understood for S. pneumoniae.