Molecular Analysis Of Salmonella Enterica Serovar Typhi Isolates Using Pulsed-Field Gel Electrophoresis; Comparison Between Acute And Carriers Of Typhoid Fever

Typhoid fever is a systemic disease caused by S.Typhi, a Gram negative bacterium that infects exclusively humans. The disease is endemic in Kelantan, which has the highest incidence in Malaysia. Despite the endemicity, not much information is known regarding the type of S.Typhi strains and its distribution in this region. Thus, this study was conducted to ascertain retrospectively the genetic diversity and distribution of S.Typhi strains isolated from patients with acute typhoid, asymptomatic carriers and environmental samples in Kelantan, between the year 2002 and 2009

Livestock and environment as potential sources and reservoirs for multi-drug resistant Escherichia coli in Malaysia: A Systematic Review

Pathogenic Escherichia coli (E. coli) is a significant foodborne pathogen that poses a serious global public health risk. These pathogenic strains of E. coli can be found in various environments such as soil, water, livestock, livestock products, and humans. This review aims to evaluate the role of livestock and the environment as potential sources and reservoirs of pathogenic E. coli in Malaysia over the past two decades. A systematic search was conducted on PubMed, Scopus, Web of Science, and Google Scholar databases using standardized keywords (Escherichia coli, Livestock, Abattoir workers, Farm workers, and Malaysia) to identify relevant original research articles published between 2001 and 2023 and our systematic review protocol was published in Prospero (Registration number: CRD42023433199). A total of 20 eligible articles were included in this review. The prevalence of multi-drug resistant E. coli among livestock production system and the environment, ranged from 4% to 100%. E. coli strains isolated from livestock production systems and environment in Malaysia exhibited high potential for pathogenicity, with diverse enterotoxins, genes associated with antimicrobial resistance, and virulence factors. Phylogroup B and D were noted among the E. coli isolates indicating that the strains in Malaysia are highly virulent and extra-intestinal. High levels of resistance to antimicrobials particularly ESBL and colistin which are last resort antimicrobials were noted. Butchering or processing of livestock, contamination of plants via contaminated waterways or livestock manure are the main sources and reservoir for E. coli to spread in Malaysia. Continued surveillance, monitoring and a comprehensive 'One Health' approach are recommended to effectively prevent and control livestock drug-resistant E.coli strains throughout the country

Antimicrobial polymers:The potential replacement of existing antibiotics?

Antimicrobial resistance is now considered a major global challenge; compromising medical advancements and our ability to treat infectious disease. Increased antimicrobial resistance has resulted in increased morbidity and mortality due to infectious diseases worldwide. The lack of discovery of novel compounds from natural products or new classes of antimicrobials, encouraged us to recycle discontinued antimicrobials that were previously removed from routine use due to their toxicity, e.g., colistin. Since the discovery of new classes of compounds is extremely expensive and has very little success, one strategy to overcome this issue could be the application of synthetic compounds that possess antimicrobial activities. Polymers with innate antimicrobial properties or that have the ability to be conjugated with other antimicrobial compounds create the possibility for replacement of antimicrobials either for the direct application as medicine or implanted on medical devices to control infection. Here, we provide the latest update on research related to antimicrobial polymers in the context of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens. We summarise polymer subgroups: compounds containing natural peptides, halogens, phosphor and sulfo derivatives and phenol and benzoic derivatives, organometalic polymers, metal nanoparticles incorporated into polymeric carriers, dendrimers and polymer-based guanidine. We intend to enhance understanding in the field and promote further work on the development of polymer based antimicrobial compounds

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

BACKGROUND:Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS:Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS:Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators

Targeting the Bacterial Protective Armour; Challenges and Novel Strategies in the Treatment of Microbial Biofilm

Infectious disease caused by pathogenic bacteria continues to be the primary challenge to humanity. Antimicrobial resistance and microbial biofilm formation in part, lead to treatment failures. The formation of biofilms by nosocomial pathogens such as Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Klebsiella pneumoniae (K. pneumoniae) on medical devices and on the surfaces of infected sites bring additional hurdles to existing therapies. In this review, we discuss the challenges encountered by conventional treatment strategies in the clinic. We also provide updates on current on-going research related to the development of novel anti-biofilm technologies. We intend for this review to provide understanding to readers on the current problem in health-care settings and propose new ideas for new intervention strategies to reduce the burden related to microbial infections

Prevalence of Antimicrobial Resistance (AMR) <em>Salmonella spp</em>. and <em>Escherichia coli</em> Isolated From Broilers in East Coast Malaysia

Abstract:Salmonella species (spp) and Escherichia coli (E. coli) are the most common infectious pathogens in poultry. Antimicrobials were given either for the treatment or growth promoters that can increase the possibility of emergence of bacterial resistance towards antimicrobials. The aim of this study was to determine the prevalence of antimicrobial resistant (AMR) Salmonella spp and E. coli isolated from a sample of broiler farms in East Coast Malaysia from 2018-2019. A total of 384 cloacal swabs were collected from broilers farms in Kelantan, Terengganu, and Pahang. The bacteria were isolated and confirmed by bacteriological and serological methods. Following that, confirmed isolates were subjected to antimicrobial susceptibility test. Salmonella spp and E. coli were recovered from the cloacal swabs samples with the overall prevalence of 6.5% and 51.8% respectively. In Kelantan, Terengganu and Pahang, the prevalence of Salmonella spp were 7%, 6.5% and 5.8% respectively, while the prevalence for E. coli were 50%, 48.3% and 58% respectively. Salmonella spp and E. coli displayed resistance towards the following antimicrobials: erythromycin (100% for both pathogens), chloramphenicol (76.2%, 84.5%), tetracycline (62%, 94.6%), ampicillin (47.7%, 87%), sulfamethoxazole/trimethoprim (42.9%, 83.3%), ciprofloxacin (4.8%, 23.8%), nalidixic acid (9.6%, 60.7%), streptomycin (19%,66%), and kanamycin (28.6%,57%), cephalotin (0%, 11%), gentamicin (0%, 20.2%) respectively. No resistance were recorded towards colistin for both pathogens. Multidrug resistance (MDR) was recorded in 82% of Salmonella spp and 100% of E. coli. These findings demonstrate the high prevalence of MDR Salmonella spp. and E. coli in broiler farms in East coast Malaysia. This could be attributed to the excessive use of antimicrobial agents by the poultry farm owners. Enhanced control measures and a strong monitoring system should be urgently implemented to reduce the emergence of antimicrobial resistance that is harmful to public health.</jats:p

Targeting the hard to reach: challenges and novel strategies in the treatment of intracellular bacterial infections.

Infectious diseases continue to threaten human and animal health and welfare globally, impacting millions of lives and causing substantial economic loss. The use of antibacterials has been only partially successful in reducing disease impact. Bacterial cells are inherently resilient, and the therapy challenge is increased by the development of antibacterial resistance, the formation of biofilms and the ability of certain clinically important pathogens to invade and localize within host cells. Invasion into host cells provides protection from both antibacterials and the host immune system. Poor delivery of antibacterials into host cells causes inadequate bacterial clearance, resulting in chronic and unresolved infections. In this review, we discuss the challenges associated with existing antibacterial therapies with a focus on intracellular pathogens. We consider the requirements for successful treatment of intracellular infections and novel platforms currently under development. Finally, we discuss novel strategies to improve drug penetration into host cells. As an example, we discuss our recent demonstration that the cell penetrating cationic polymer polyhexamethylene biguanide has antibacterial activity against intracellular Staphylococcus aureus

Antimicrobial Peptides: Bringing Solution to the Rising Threats of Antimicrobial Resistance in Livestock

Antimicrobial therapy is the most applied method for treating and preventing bacterial infection in livestock. However, it becomes less effective due to the development of antimicrobial resistance (AMR). Therefore, there is an urgent need to find new antimicrobials to reduce the rising rate of AMR. Recently, antimicrobial peptides (AMPs) have been receiving increasing attention due to their broad-spectrum antimicrobial activity, rapid killing activities, less toxicity, and cell selectivity. These features make them potent and potential alternative antimicrobials to be used in animals. Here, we discuss and summarize the AMPs in animals, classification, structures, mechanisms of action, and their potential use as novel therapeutic alternative antimicrobials to tackle the growing AMR threat.</jats:p

Phylogenetically Diverse Escherichia coli Strains from Chicken Coharbor Multiple Carbapenemase-Encoding Genes (blaNDM-blaOXA-blaIMP)

Carbapenem-resistant Enterobacteriaceae (CRE) has been a public health risk in several countries, and recent reports indicate the emergence of CRE in food animals. This study was conducted to investigate the occurrence, resistance patterns, and phylogenetic diversity of carbapenem-resistant E. coli (CREC) from chicken. Routine bacteriology, PCR detection of E. coli species, multiplex PCR to detect carbapenemase-encoding genes, and phylogeny of CRE E. coli were conducted. The results show that 24.36% (19/78) were identified as CREC based on the phenotypic identifications of which 17 were positive for the tested carbapenemases genes. The majority, 57.99% (11/19), of the isolates harbored multiple carbapenemase genes. Four isolates harbored all blaNDM, blaOXA, and blaIMP, and five and two different isolates harbored blaNDM and blaOXA and blaOXA and blaIMP, respectively. The meropenem, imipenem, and ertapenem MIC values for the isolates ranged from 2 μg/mL to ≥256 μg/mL. Phylogenetic grouping showed that the CREC isolates belonged to five different groups: groups A, B1, C, D, and unknown. The detection of CREC in this study shows that it has become an emerging problem in farm animals, particularly, in poultry farms. This also implies the potential public health risks posed by CRE from chicken to the consumers.</jats:p