Mycobacterium tuberculosis (Mtb), an acid-fast bacillus that causes Tuberculosis (TB), is a pathogen that caused 1.5 million deaths in 2020. As per WHO estimates, another 4.1 million people are ...suffering from latent TB, either asymptomatic or not diagnosed, and the frequency of drug resistance is increasing due to intrinsically linked factors from both host and bacterium. For instance, poor access to TB diagnosis and reduced treatment in the era of the COVID-19 pandemic has resulted in more TB deaths and an 18% reduction in newly diagnosed cases of TB. Additionally, the detection of Mtb isolates exhibiting resistance to multiple drugs (MDR, XDR, and TDR) has complicated the scenario in the pathogen's favour. Moreover, the conventional methods to detect drug resistance may miss mutations, making it challenging to decide on the treatment regimen. However, owing to collaborative initiatives, the last two decades have witnessed several advancements in both the detection methods and drug discovery against drug-resistant isolates. The majority of them belong to nucleic acid detection techniques. In this review, we highlight and summarize the molecular mechanism underlying drug resistance in Mtb, the recent advancements in resistance detection methods, and the newer drugs used against drug-resistant TB.
The novel coronavirus-19 (SARS-CoV-2), has infected numerous individuals worldwide, resulting in millions of fatalities. The pandemic spread with high mortality rates in multiple waves, leaving ...others with moderate to severe symptoms. Co-morbidity variables, including hypertension, diabetes, and immunosuppression, have exacerbated the severity of COVID-19. In addition, numerous efforts have been made to comprehend the pathogenic and host variables that contribute to COVID-19 susceptibility and pathogenesis. One of these endeavours is understanding the host genetic factors predisposing an individual to COVID-19. Genome-Wide Association Studies (GWAS) have demonstrated the host predisposition factors in different populations. These factors are involved in the appropriate immune response, their imbalance influences susceptibility or resistance to viral infection. This review investigated the host genetic components implicated at the various stages of viral pathogenesis, including viral entry, pathophysiological alterations, and immunological responses. In addition, the recent and most updated genetic variations associated with multiple host factors affecting COVID-19 pathogenesis are described in the study.
Dengue fever (DF) continues to be one of the tropical and subtropical health concerns. Its prevalence tends to increase in some places in these regions. This disease is caused by the dengue virus ...(DENV), which is transmitted through the mosquitoes Aedes aegypti and A. albopictus. The treatment of DF to date is only supportive and there is no definitive vaccine to prevent this disease. The non-structural DENV protein, RNA-dependent RNA Polymerase (RdRp), is involved in viral replication. The RdRp-derived peptides can be used in the construction of a universal dengue vaccine. These peptides can be utilized as epitopes to induce immunity. This study was an in silico evaluation of the affinity of the potential epitope for the universal dengue vaccine to dendritic cells and the bonds between the epitope and the dendritic cell receptor. The peptide sequence MGKREKKLGEFGKAKG generated from dengue virus subtype 2 (DENV-2) RdRp was antigenic, did not produce allergies, was non-toxic, and had no homology with the human genome. The potential epitope-based vaccine MGKREKKLGEFGKAKG binds stably to dendritic cell receptors with a binding free energy of −474,4 kcal/mol. This epitope is anticipated to induce an immunological response and has the potential to serve as a universal dengue virus vaccine candidate.
(
) is a major causative agent of mastitis and is resistant to many antibiotics. Thus, there is a need to characterize the genetic determinants of
erythromycin resistance, such as
,
and
. The current ...study aimed to determine the phenotypic and genotypic erythromycin resistance profile and relatedness of
recovered from bovine mastitis and humans in close contact. A total of 14 mastitis-infected buffalo milk samples and 16 samples from their respective milkers were collected from different farms of Lahore, Pakistan. The antibiotic resistance profile was determined through the disk diffusion test. The overall prevalence of
in mastitis-affected buffaloes was found to be 75%, of which 52.1% were resistant to erythromycin and 42.8% to clindamycin.
isolates recovered from milker nasal samples showed 56.25% resistance to erythromycin and 44% resistance to clindamycin. Genotypic antibiotic resistance profiles were determined from 14 milk samples through PCR. Overall, eight (52.1%), three (21.4%) and five (35.7%)
isolates were positive for the
,
and
genes, respectively. Moreover, 16 milker nasal
isolates were also tested for the presence of
,
and
genes. The
,
and
genes were observed in nine(56.7%), five (31.3%) and seven (43.7%) isolates, respectively. A significant association was shown between phenotypic and genotypic erythromycin resistance. The results indicate both that there are sufficient genetic similarities, and the actual transmission of erythromycin resistance genes between these two hosts of
Monkeypox virus (MPXV) core cysteine proteinase (CCP) is one of the major drug targets used to examine the inhibitory action of chemical moieties. In this study, an in silico technique was applied to ...screen 1395 anti-infective compounds to find out the potential molecules against the MPXV-CCP. The top five hits were selected after screening and processed for exhaustive docking based on the docked score of ≤ -9.5 kcal/mol. Later, the top three hits based on the exhaustive-docking score and interaction profile were selected to perform MD simulations. The overall RMSD suggested that two compounds, SC75741 and ammonium glycyrrhizinate, showed a highly stable complex with a standard deviation of 0.18 and 0.23 nm, respectively. Later, the MM/GBSA binding free energies of complexes showed significant binding strength with ΔG
from -21.59 to -15 kcal/mol. This report reported the potential inhibitory activity of SC75741 and ammonium glycyrrhizinate against MPXV-CCP by competitively inhibiting the binding of the native substrate.
The scale at which the SARS-CoV-2/COVID-19 pandemic has spread remains enormous. Provided the genetic makeup of the virus and humans is readily available, the quest for knowing the mechanism and ...epidemiology continues to prevail across the entire scientific community. Several aspects, including immunology, molecular biology, and host-pathogen interaction, are continuously being dug into for preparing the human race for future pandemics. The exact reasons for vast differences in symptoms, pathophysiological implications of COVID-infections, and mortality differences remain elusive. Hence, researchers are also looking beyond traditional genomics, proteomics, and transcriptomics approach, especially entrusting the environmental regulation of the genetic landscape of COVID-human interactions. In line with these questions lies a critical process called epigenetics. The epigenetic perturbations in both host and parasites are a matter of great interest to unravel the disparities in COVID-19 mortalities and pathology. This review provides a deeper insight into current research on the epigenetic landscape of SARS-CoV-2 infection in humans and potential targets for augmenting the ongoing investigation. It also explores the potential targets, pathways, and networks associated with the epigenetic regulation of processes involved in SARS-CoV-2 pathology.
Nontyphoidal Salmonella (NTS) species are important food-borne pathogens that cause gastroenteritis and bacteremia, and are responsible for a huge global burden of morbidity and mortality. The aim of ...this study was to investigate the prevalent serogroups and antibiotic resistance of NTS in our region.
We reviewed the serogroup distribution and antimicrobial susceptibility patterns of NTS strains obtained from 158 stool specimens of patients with acute diarrheal infection attending the outpatient and inpatient department at a university hospital in the Eastern Province of Saudi Arabia in the period from September, 2008 to April, 2011. A retrospective analysis of the 158 patients with NTS infection was conducted to determine the most prevalent NTS serogroups causing acute gastroenteritis and their antimicrobial susceptibility patterns.
At this teaching hospital, a total of 17,436 fecal samples were analyzed during the 2008-2011 study period. Of these specimens, 158 tested positive for NTS, giving an overall prevalence of 9.06 per 1,000. Of 158 NTS cases, serogroup D1 (25.3%) was the most prevalent, followed by serogroup B (19.6%), and serogroup C1 (18.9). One third of all NTS serogroup strains tested were resistant to tetracycline. The NTS strains showed resistance to ampicillin (31.3%), amoxicillin/clavulanic acid (29.9%), trimethoprim/sulfamethoxazole (20.9%), and cefotaxime (14.93%).
The findings of this study support the concern that use of antibiotics in animal feeds may contribute to acquisition of resistance in food-borne bacteria, such as Salmonella. Our study also concludes that the prevalence of NTS in the Eastern Province of Saudi Arabia is very low compared with other studies worldwide.
(1) Background: The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus. It was called monkeypox because it ...was first discovered in monkeys, in a Danish laboratory, in 1958. However, the actual reservoir for MPV is still unknown. (2) Methods and Results: We have reviewed the existing literature on the options for Monkeypox virus. There are three available vaccines for orthopoxviruses—ACAM2000, JYNNEOS, and LC16—with the first being a replicating vaccine and the latter being non- or minimally replicating. (3) Conclusions: Smallpox vaccinations previously provided coincidental immunity to MPV. ACAM2000 (a live-attenuated replicating vaccine) and JYNNEOS (a live-attenuated, nonreplicating vaccine) are two US FDA-approved vaccines that can prevent monkeypox. However, ACAM2000 may cause serious side effects, including cardiac problems, whereas JYNNEOS is associated with fewer complications. The recent outbreaks across the globe have once again highlighted the need for constant monitoring and the development of novel prophylactic and therapeutic modalities. Based on available data, there is still a need to develop an effective and safe new generation of vaccines specific for monkeypox that are killed or developed into a mRNA vaccine before monkeypox is declared a pandemic.
Staphylococcus aureus (S. aureus) is a major causative agent of mastitis and is resistant to many antibiotics. Thus, there is a need to characterize the genetic determinants of S. aureus erythromycin ...resistance, such as ermA, ermB and ermC. The current study aimed to determine the phenotypic and genotypic erythromycin resistance profile and relatedness of S. aureus recovered from bovine mastitis and humans in close contact. A total of 14 mastitis-infected buffalo milk samples and 16 samples from their respective milkers were collected from different farms of Lahore, Pakistan. The antibiotic resistance profile was determined through the disk diffusion test. The overall prevalence of S. aureus in mastitis-affected buffaloes was found to be 75%, of which 52.1% were resistant to erythromycin and 42.8% to clindamycin. S. aureus isolates recovered from milker nasal samples showed 56.25% resistance to erythromycin and 44% resistance to clindamycin. Genotypic antibiotic resistance profiles were determined from 14 milk samples through PCR. Overall, eight (52.1%), three (21.4%) and five (35.7%) S. aureus isolates were positive for the ermA, ermB and ermC genes, respectively. Moreover, 16 milker nasal S. aureus isolates were also tested for the presence of ermA, ermB and ermC genes. The ermA, ermB and ermC genes were observed in nine(56.7%), five (31.3%) and seven (43.7%) isolates, respectively. A significant association was shown between phenotypic and genotypic erythromycin resistance. The results indicate both that there are sufficient genetic similarities, and the actual transmission of erythromycin resistance genes between these two hosts of S. aureus.
The antibacterial activity of Whey Milk and its fractions were studied against one hundred bacteria strains isolated and screened from various patients at the University Hospital of Zagazig, Sharkia ...Province, Egypt. F2 fraction of Whey Milk has shown the highest degree of antibacterial activity against the pathogenic bacteria A63 isolated from the wound. Buffalo whey (BW) was hydrolyzed with papain followed by fractionation using size exclusion chromatography (SEC). The fractionation profile of BWH showed three major peaks in Size exclusion chromatography, SECF1, SECF2, and SECF3 after 3h. F2 is the most active fraction and has faster migration than HP, F1, and F3 and may have higher positive charges on Urea-PAGE towards the cathode direction. FTIR spectrum analysis of the F2 fraction of whey protein demonstrates the occurrence of distinctive functional groups, such as Alkanes, alcohols, phenols, flavonoids, alkenes, anhydrides, and halo compounds. The biochemical characters and the 1.5 Kb 16S RNA gene's nucleotide sequence of the most potent stain showed 99% similarity with Staphylococcus pasteuri. Our results showed that the ability of nanoparticles of whey to inhibit pathogenic bacteria decreases compared to raw whey and its fractions. Cellular deformation and partial and total lysis of cell components were seen in Staphylococcus pasteuri treated with whey F2 fraction under Transmission Electron Microscopy (TEM).
PDF
