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Oral vaccination with Lactococcus lactis expressing the Vibrio cholerae Wzm protein to enhance mucosal and systemic immunity

Zamri HF, Shamsudin MN, Rahim RA, Neela V

Vaccine, 2012 May 2;30(21):3231-8.
PMID: 22426330 DOI: 10.1016/j.vaccine.2012.02.012

A gene associated with lipopolysaccharide (LPS) transport was cloned from a local clinical Vibrio cholerae O1 strain of the Ogawa serotype by using the Lactococcus lactis nisin-controlled expression (NICE) system. The V. cholerae wzm gene, which codes for an integral membrane transporter protein, was expressed and targeted to the cytoplasmic membrane, and was crudely isolated through simple centrifugation and SDS solubilization. To examine seroreactivity of this construct, rabbits were orally fed with 10(9) cfu/ml of live, recombinant L. lactis carrying the wzm gene, induced with nisin prior to administration. Recombinant plasmids were retrieved from L. lactis cultured directly from stool samples of inoculated rabbits. Reverse-transcriptase PCR of wzm using the retrieved plasmids confirmed transcription of this gene, indicating viability and stability of the recombinants in vivo. The L. lactis-Wzm construct elicited substantial levels of IgG and sIgA, and challenge with virulent V. cholerae O1 evoked severe diarrhoea in the naive, non-immunised control group, but not in those fed with either recombinant or non-recombinant L. lactis. Oral administration with recombinant L. lactis expressing the V. cholerae wzm gene increases both systemic and mucosal immunity, whereas L. lactis itself appears capable of protecting against the diarrhoeal symptoms caused by V. cholerae. Wzm is a conserved membrane protein associated with the LPS endotoxin, and together with the food-grade L. lactis, represent an attractive target for the development of a safer, live anti-infective therapy against V. cholerae.
Fulltext Distribution, Prevalence, and Antibiotic Susceptibility Profiles of Infectious Noncholera Vibrio Species in Malaysia

Hassan M, Mohd Ali MR, Zamri HF, Nor Amdan NA, Azmai MNA, Maniam S, et al.

J Trop Med, 2023;2023:2716789.
PMID: 37274080 DOI: 10.1155/2023/2716789

BACKGROUND: The noncholera Vibrio spp. which cause vibriosis are abundantly found in our water ecosystem. These bacteria could negatively affect both humans and animals. To date, there is a paucity of information available on the existence and pathogenicity of this particular noncholera Vibrio spp. in Malaysia in comparison to their counterpart, Vibrio cholera.
METHODS: In this study, we extracted retrospective data from Malaysian surveillance database. Analysis was carried out using WHONET software focusing noncholera Vibrio spp. including Vibrio parahaemolyticus, Vibrio vulnificus, Vibrio fluvialis, Vibrio alginolyticus, Vibrio hollisae (Grimontia hollisae), Vibrio mimicus, Vibrio metschnikovii, and Vibrio furnissii.
RESULTS: Here, we report the first distribution and prevalence of these species isolated in Malaysia together with the antibiotic sensitivity profile based on the species. We found that V. parahaemolyticus is the predominant species isolated in Malaysia. Noticeably, across the study period, V. fluvialis is becoming more prevalent, as compared to V. parahaemolyticus. In addition, this study also reports the first isolation of pathogenic V. furnissii from stool in Malaysia.
CONCLUSION: These data represent an important step toward understanding the potential emergence of noncholera Vibrio spp. outbreaks.
Fulltext Adaptation of an in vitro one-compartment pharmacodynamic chemostat for testing efficacy of ceftazidime against Burkholderia pseudomallei outside a BSL3 facility

Zamri HF, Mohd Ali MR, Sha'ari AII, Mohd Mazalan NH, Ahmad N, Nor Amdan NA, et al.

MethodsX, 2025 Jun;14:103167.
PMID: 39897649 DOI: 10.1016/j.mex.2025.103167

Non-clinical pharmacokinetic-pharmacodynamic (PKPD) models are crucial in the initial design of drug-dosage regimens and in drug development but has rarely been employed for testing high-risk organisms due to stringent handling procedures. Burkholderia pseudomallei is classified as a Tier 1 select agent with international guidelines recommending this organism to be handled within a biosafety level 3 (BSL3) facility. Unfortunately, BSL3 facilities are not widely available in low-resource settings. This paper describes a detailed guide for setting up an in vitro pharmacodynamic infection model specific for testing B. pseudomallei outside BSL 3 laboratory. Briefly in this study,•All procedures involving active handling of live B. pseudomallei cultures were performed strictly inside a class II BSC in BSL-2 plus negative airflow laboratory.•The model was set to simulate B. pseudomallei-bacteremia treated with ceftazidime, a 1st-line anti-melioidosis drug with an approximate 2-hour half-life. Model validation was performed by simulating ceftazidime half-life.•For the pharmacodynamic study, ceftazidime was given as bolus injections at 8-hour intervals into the central culture chamber containing actively growing B. pseudomallei.
Fulltext Predominance of SCCmec type IV in community-acquired meticillin-resistant Staphylococcus aureus (MRSA) in multi-centre Malaysian hospitals

Nor Amdan NA, Zamri HF, Mohd Ali MR, Dahalan NA, Anak Maling DR, Wan Hamdan WAF, et al.

J Hosp Infect, 2024 Jan;143:113-114.
PMID: 37979625 DOI: 10.1016/j.jhin.2023.10.023