Biology subjects

Fakoya, B.

Publications and source records attributed to Fakoya, B..

6 recordsLinked to original sources

bioRxiv2025

Vibrio cholerae serotype impacts pathogenicity

The O1 serogroup of Vibrio cholerae has caused all cholera pandemics and for over a century V. cholerae O1 outbreak strains have been characterized by their serotype. The two V. cholerae serotypes differ by the presence (Ogawa) or absence (Inaba) of methylation of the terminal sugar on the lipopolysaccharide O1-antigen. Serotype switching often occurs during epidemics and has historically been attributed to the pathogen adapting to immune pressures. Here we address the impact of serotype on V. cholerae pathogenicity using otherwise isogenic Ogawa and Inaba versions of several clinical V. cholerae O1 isolates. Our findings indicate that O1 antigen methylation in Ogawa strains promotes V. cholerae colonization, infectivity and resistance to antimicrobial peptides. We propose that methylation of the O1 antigen elevates colonization by shielding the bacterium from cationic antimicrobial peptides at the pH of the small intestine. These observations provide insights into the biological significance of the V. cholerae O1 serotypes.

microbiology↗

bioRxiv2021

Non-toxigenic Vibrio cholerae challenge strains for evaluating vaccine efficacy and inferring mechanisms of protection

Human challenge studies are instrumental for testing cholera vaccines, but these studies use outdated strains and require inpatient facilities. Here, we created next-generation isogenic Ogawa and Inaba V. cholerae challenge strains (ZChol strains) derived from a contemporary Zambian clinical isolate representative of current dominant pandemic V. cholerae. To minimize the risk of severe diarrhea these strains were rendered non-toxigenic, since antibody responses which limit V. cholerae colonization are the primary mechanism of immune protection. These strains did not cause diarrhea in infant mice and proved to accurately gauge reduction in intestinal colonization mediated by effective vaccination. They are also valuable as targets for measuring vibriocidal antibody responses. Using barcoded ZChol strains, we discovered that vaccination tightens the infection bottleneck without restricting pathogen expansion in vivo. ZChol strains have the potential to enhance the safety, relevance, and scope of future cholera vaccine challenge studies and be valuable reagents for studies of immunity to cholera.

microbiology↗

bioRxiv2021

Proteomic interrogation of the pathogen-host interface in cholera

The microbial cell surface is a critical site of microbe-host interactions that often control infection outcomes. Here, using the infant rabbit model of cholera, which provides an abundant source of in vivo Vibrio cholerae cells and diarrheal fluid, we investigated the proteomic composition of this interface. Bulk diarrheal fluid proteomes revealed that cholera toxin accounts for the vast majority of the host proteins present during infection. We developed a surface biotinylation protocol to purify and quantify both bacterial and host proteins present on the surface of diarrheal fluid-derived V. cholerae. We found that SP-D, a toxin-dependent host protein that directly binds the V. cholerae surface, is a novel intestinal defense factor. Other V. cholerae-bound host proteins also bound distinct taxa of the murine intestinal microbiota. Proteomic investigation of the microbial surface-host interface should be a valuable tool for probing microbe-host interactions and their influence on homeostasis and infection.

microbiology↗

bioRxiv2020

Dissecting serotype-specific contributions to live oral cholera vaccine efficacy

The O1 serogroup of Vibrio cholerae causes pandemic cholera and is divided into Ogawa and Inaba serotypes. The O-antigen is V. choleraes immunodominant antigen, and the two serotypes, which differ by the presence or absence of a terminally methylated O-antigen, likely influence development of immunity to cholera and oral cholera vaccines (OCVs). However, there is no consensus regarding the relative immunological potency of each serotype, in part because previous studies relied on genetically heterogenous strains. Here, we engineered matched serotype variants of a live OCV candidate, HaitiV, and used a germ-free mouse model to evaluate the immunogenicity and protective efficacy of each vaccine serotype. By combining vibriocidal antibody quantification with single and mixed strain infection assays, we found that all three HaitiV variants - InabaV, OgawaV, and HikoV (bivalent Inaba/Ogawa) - were immunogenic and protective, suggesting the impact of O1 serotype variation on OCV function may be minimal. The potency of OCVs was found to be challenge strain-dependent, emphasizing the importance of appropriate strain selection for cholera challenge studies. Our findings and experimental approaches will be valuable for guiding the development of live OCVs and oral vaccines for additional pathogens.

microbiology↗

bioRxiv2020

Transient intestinal colonization by a live-attenuated oral cholera vaccine induces protective immune responses in streptomycin-treated mice

Current mouse models for evaluating the efficacy of live oral cholera vaccines (OCVs) have important limitations. Conventionally raised adult mice are resistant to intestinal colonization by Vibrio cholerae, but germ-free mice can be colonized and have been used to study OCV immunogenicity. However, germ free animals have impaired immune systems and intestinal physiology; also, live OCVs colonize germ free mice for many months, which does not mimic the clearance kinetics of live OCVs in humans. Here, we leverage antibiotic-treated, conventionally raised adult mice to study the effects of transient intestinal colonization by a live OCV V. cholerae strain. In a single dose vaccination regimen, we found that HaitiV, a live-attenuated OCV candidate, was cleared by streptomycin treated adult mice within a week after oral inoculation. This transient colonization elicited far stronger adaptive immune correlates of protection against cholera than did inactivated whole-cell HaitiV. Infant mice from HaitiV vaccinated dams were also significantly protected from choleric disease than pups from inactivated-HaitiV dams. Our findings establish the benefits of antibiotic treated mice for live OCV studies as well as its limitations and underscore the immunogenicity of HaitiV. ImportanceOral cholera vaccines (OCVs) are being deployed to combat cholera but current killed OCVs require multiple doses and show little efficacy in young children. Live OCVs have the potential to overcome these limitations but small animal models for testing OCVs have shortcomings. We used an antibiotic treatment protocol for conventional adult mice to study the effects of short-term colonization by a single dose of HaitiV, a live OCV candidate. Vaccinated mice developed vibriocidal antibodies against V. cholerae and delivered pups that were resistant to cholera, whereas mice vaccinated with inactivated HaitiV did not. These findings demonstrate HaitiVs immunogenicity and suggest that this antibiotic treatment protocol will be useful for evaluating the efficacy of live OCVs.

microbiology↗

bioRxiv2019

Oral immunization with a probiotic cholera vaccine induces broad protective immunity against Vibrio cholerae colonization and disease in mice

Oral cholera vaccines (OCVs) are being increasingly employed, but current killed formulations generally require multiple doses and lack efficacy in young children. We recently developed a new live-attenuated OCV candidate (HaitiV) derived from a Vibrio cholerae strain isolated during the 2010 Haiti cholera epidemic. HaitiV exhibited an unexpected probiotic-like activity in infant rabbits, preventing intestinal colonization and disease by wild-type V. cholerae before the onset of adaptive immunity. However, it remained unknown whether HaitiV would behave similarly to other OCVs to stimulate adaptive immunity against V. cholerae. Here, we orally immunized adult germ-free female mice to test HaitiVs immunogenicity. HaitiV safely and stably colonized vaccinated mice and induced known adaptive immune correlates of cholera protection within 14 days of administration. Pups born to immunized mice were protected against lethal challenges of both homologous and heterologous V. cholerae strains. Cross-fostering experiments revealed that protection was not dependent on vaccine colonization in or transmission to the pups. These findings demonstrate the protective immunogenicity of HaitiV and support its development as a new tool for limiting cholera. Author summaryVaccines for cholera are gaining acceptance as public health tools for prevention of cholera and curtailing the spread of outbreaks. However, current killed vaccines provide minimal protection in young children, who are especially susceptible to this diarrheal disease, and do not stimulate immunity against antigens that may only be expressed by live bacteria during infection. We recently developed HaitiV, an extensively engineered live-attenuated oral cholera vaccine candidate, derived from a clinical isolate from the Haiti cholera outbreak. Here, we found that the HaitiV induces immunological correlates of protection against cholera in germ free mice and leads to protection against disease in their offspring. Protection in this model was dependent on passively acquired factors in the milk of immunized dams and not transmission or colonization of HaitiV. Coupling the immunogenicity data presented here with our previous observation that HaitiV can protect from cholera prior to the induction of adaptive immunity, suggests that HaitiV may provide both rapid-onset short-term protection from disease while eliciting stable and long-lasting immunity against cholera.

microbiology↗