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1.
J Pak Med Assoc ; 72(3): 509-515, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35320234

ABSTRACT

Staphylococcus aureus is a common gram-positive human pathogen involved in both community-acquired and nosocomial infections ranging from localised superficial lesions to food poisoning and fatal systemic infections owing to its impressive array of virulence factors responsible for attaching, colonising, invading, and avoiding host immune system. The discovery of antibiotics effectively checked the once deadly infections. However, resistance started soon after their discovery and the first methicillin-resistant strain of staphylococcus aureus was reported in the early 1960s. The most important attribute of methicillin-resistant staphylococcus aureus is its acquisition of mecA gene coding for penicillin-binding protein-2a that blocks inhibitory action on peptidoglycan cross-linking. Methicillin-resistant staphylococcus aureus presents a serious global healthcare concern being responsible for prolonged hospital stays and increased mortality. The precise information of virulence factors and resistant traits of methicillin-resistant staphylococcus aureus and their interplay in a community is key to minimize the intermixing of resistant and susceptible pathogens in the community.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Methicillin Resistance/genetics , Methicillin-Resistant Staphylococcus aureus/genetics , Staphylococcal Infections/drug therapy , Staphylococcal Infections/epidemiology , Staphylococcus aureus , Virulence
2.
Int J Pept Res Ther ; 28(1): 16, 2022.
Article in English | MEDLINE | ID: mdl-34873398

ABSTRACT

Acinetobacter baumannii is notorious for causing serious infections of the skin, lungs, soft tissues, bloodstream, and urinary tract. Despite the overwhelming information available so far, there has still been no approved vaccine in the market to prevent these infections. Therefore, this study focuses on developing a rational vaccine design using the technique of epitope mapping to curb the infections caused by A. baumannii. An outer membrane protein with immunogenic potential as well as all the properties of a good vaccine candidate was selected and used to calculate epitopes for selection on the basis of a low percentile rank, high binding scores, good immunological properties, and non-allergenicity. Thus, a 240 amino-acid vaccine sequence was obtained by manually joining all the epitopes in sequence-wise manner with the appropriate linkers, namely AAY, GPGPG, and EAAAK. Additionally, a 50S ribosomal protein L7/L12, agonist to the human innate immune receptors was attached to the N-terminus to increase the overall immune response towards the vaccine. As a result, enhanced overall protein stability, expression, immunostimulatory capabilities, and solubility of the designed construct were observed. Molecular dynamic simulations revealed the compactness and stability of the polypeptide construct. Moreover, molecular docking exhibited strong binding of the designed vaccine with TLR-4 and TLR-9. In-silico immune simulations indicated an immense increment in T-cell and B-cell populations. Bioinformatic tools also significantly assisted with optimizing codons which allowed for successful cloning of constructs into desired host vectors. Using in-silico tools to design a vaccine against A. baumannii demonstrated that this construct could pave the way for successfully combating infections caused by multidrug-resistant bacteria. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10989-021-10316-7.

3.
Folia Microbiol (Praha) ; 66(5): 809-817, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34143328

ABSTRACT

Shiga toxin-producing Escherichia coli (STEC) is an important foodborne pathogens, known to cause enteric infections especially diarrhea, mainly attributed to Shiga toxins (Stxs). The use of certain antibiotics for treating this infection is controversial, owing to an increased risk for producing Stxs (Stx 1 and Stx 2). Increased antibiotic resistance is also thought to be involved in the pathogenesis of STEC diseases. The purpose of this study was to analyze the effects of antibiotics on induction of Stx 1 and Stx 2 in clinical STEC isolates and to investigate the relationships between increased resistance and Stx production. Fifteen clinical isolates were treated with sub minimum inhibitory concentrations (Sub MIC) of clinically used antibiotics (ciprofloxacin, fosfomycin, tigecycline, and meropenem), and the changes in expression levels of stx1 and stx2 genes were estimated using qRT-PCR. The expressions of Shiga toxins were found to be increased up to 6.5- and eightfold under ciprofloxacin and tigecycline Sub MIC, respectively. Fosfomycin had weak induction effect of up to twofold, whereas meropenem had the weakest influence on such expression. Resistant isolates were found to be more prone to increased expression of toxins.


Subject(s)
Gene Expression Regulation, Bacterial , Shiga Toxin 1 , Shiga Toxin 2 , Shiga-Toxigenic Escherichia coli , Anti-Bacterial Agents/pharmacology , Escherichia coli Infections/microbiology , Gene Expression Profiling , Gene Expression Regulation, Bacterial/drug effects , Humans , Shiga Toxin 1/genetics , Shiga Toxin 2/genetics , Shiga-Toxigenic Escherichia coli/drug effects , Shiga-Toxigenic Escherichia coli/genetics
4.
J Pak Med Assoc ; 68(5): 768-772, 2018 May.
Article in English | MEDLINE | ID: mdl-29885179

ABSTRACT

Enterococci are known as opportunistic pathogens and today are accepted as leading cause of nosocomial infections. Various enterococcal species have been identified, but the major two which cause human diseases are enterococcus faecalis and enterococcus faecium. Most common and important infections caused by them are bacteraemia, endocarditis, urinary tract infections, surgical wound infections, intra-abdominal and intra-pelvic infections. Over the last two decades the emergence of vancomycin-resistant enterococci is alarming because of high mortality rate. Being resistant nosocomial infectious agents, vancomycin-resistant enterococci are a serious threat to current healthcare practices. Antibiotic resistance determinants VanA and VanB are globally reported in vancomycin-resistant enterococci clinical isolates. This paper covers a comprehensive overview of vancomycin-resistant enterococci infection epidemiology, virulence, drug resistance, its prevention and treatment.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Enterococcus faecalis/drug effects , Enterococcus faecium/drug effects , Gram-Positive Bacterial Infections/drug therapy , Vancomycin Resistance , Vancomycin-Resistant Enterococci/drug effects , Vancomycin/therapeutic use , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Carbon-Oxygen Ligases/genetics , Enterococcus faecalis/genetics , Enterococcus faecalis/pathogenicity , Enterococcus faecium/genetics , Enterococcus faecium/pathogenicity , Humans , Vancomycin/pharmacology , Vancomycin Resistance/genetics , Vancomycin-Resistant Enterococci/genetics , Vancomycin-Resistant Enterococci/pathogenicity
5.
Open Life Sci ; 13: 553-560, 2018 Jan.
Article in English | MEDLINE | ID: mdl-33817126

ABSTRACT

Enterococcus faecium, is an important nosocomial pathogen with increased incidence of multidrug resistance (MDR) - specifically Vancomycin resistance. E. faecium constitutes the normal microbiota of the human intestine as well as exists in the hospitals and sewage, thus making the microorganism difficult to eliminate. Phage therapy has gained attention for controlling bacterial MDR infections and contaminations. We have successfully isolated from waste water and characterized a lytic bacteriophage STH1 capable of targeting Vancomycin resistant Enterococcus faecium (VREF) with high specificity. The phage was isolated from sewage water of a hospital at district Dera Ismail Khan, Pakistan. Initial characterization showed that magnesium and calcium ions significantly increased phage adsorption to the host. One step growth experiment showed a latent period of 18 min with burst size of 334 virions per cell. Optimal temperature and pH of the phage was 37°C and 7.0, respectively. Phage application to host strain grown in milk and water (treated and untreated) showed that the phage efficiently controlled bacterial growth. The study suggests that the phage STH1 can serve as potential control agent for E. faecium infections in medical facilities and in other environmental contaminations.

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