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1.
Dig Dis ; 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38493766

ABSTRACT

BACKGROUND: Helicobacter pylori (H. pylori) infection is the most prevalent type of bacterial infection. Current guidelines from different regions of the world neglect specific African conditions and requirements. The African Helicobacter and Microbiota Study Group (AHMSG), founded in 2022, aims to create an Africa-specific consensus report reflecting Africa-specific issues. SUMMARY: Eighteen experts from nine African countries and two European delegates supported by nine African collaborators from eight other countries prepared statements on the most important African issues in four working groups: (1) epidemiology, (2) diagnosis, (3) indications and prevention, and (4) treatment. Limited resources, restricted access to medical systems, and underdeveloped diagnostic facilities differ from those of other regions. The results of the individual working groups were presented for the final consensus voting, which included all board members. KEY MESSAGES: There is need for further studies on H. pylori prevalence in Africa, with diagnosis hinged on specific African situation. Treatment of H. pylori in the African setting should be based on accessibility and reimbursement, while indication and prevention should be defined in specific African countries.

2.
Infect Dis Poverty ; 13(1): 10, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38297349

ABSTRACT

BACKGROUND: Anthrax is a non-contagious zoonotic disease caused by the Gram-positive, spore-forming bacterium Bacillus anthracis. Infection is common in livestock and wild animals such as cattle, goats, sheep, camels, and antelopes. In humans, anthrax may occur after contact with contaminated carcasses or animal products like milk and meat. The best method to prevent anthrax in people is to ensure livestock are vaccinated, which significantly limits the risk of zoonotic spread to humans. However, the rate of vaccination of domesticated animals kept by nomadic pastoralists in West Africa is low. These groups regularly cross over national boundaries with their grazing herds. Nigeria is a country that historically has done comparatively well to contain this public health threat. However, in 2023 several outbreaks of human disease appear linked to the consumption of anthrax-contaminated animal products brought into Nigeria by pastoralists from neighboring countries. Clinical manifestations include skin sores or ulcers, nausea, vomiting, and fever. This article aims to raise awareness of recent outbreaks of anthrax in West Africa and to call for a renewed focus on measures to combat this neglected public health concern to the region. MAIN BODY: The imperative to pinpoint pivotal issues relating to the ongoing emergence of anthrax cases in Nigeria cannot be overstated. By delving into the prevalence of anthrax in both livestock and human populations residing along Nigeria's borders, unraveling the genetic diversity and potential sources of B. anthracis strains, and identifying the primary animal host(s) responsible for transmission, we stand to enhance our understanding of this critical issue. Furthermore, investigating the multifaceted factors contributing to anthrax transmission, assessing community knowledge and practices, mapping common migratory routes of pastoralists, and formulating targeted intervention strategies tailored to the challenges of border communities, are each crucial steps towards effective control and prevention. CONCLUSION: Closing these knowledge gaps on anthrax is not only essential for safeguarding both animal and human health but also for fostering sustainable and resilient communities. Addressing research questions on these interdisciplinary concerns will undoubtedly pave the way for informed decision-making, proactive measures, and a more secure future for Nigeria and its border regions.


Subject(s)
Anthrax , Bacillus anthracis , Cattle , Humans , Animals , Sheep , Anthrax/epidemiology , Anthrax/prevention & control , Anthrax/veterinary , Nigeria/epidemiology , Disease Outbreaks/veterinary , Bacillus anthracis/genetics , Zoonoses/epidemiology , Zoonoses/prevention & control , Livestock , Goats
3.
Eur J Microbiol Immunol (Bp) ; 13(4): 107-124, 2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38051352

ABSTRACT

Campylobacter infections and campylobacteriosis-associated post-infectious sequelae are a significant global health burden that needs to be addressed from a specific African perspective. We conducted a comprehensive literature search on NCBI PubMed to compile a comprehensive narrative review article on Campylobacter infections in Africa, focusing on key aspects in human and veterinary medicine as well as food hygiene. We specifically focused on the epidemiology of enteropathogenic Campylobacter spp. in sub-Saharan and North Africa considering antimicrobial susceptibility. The most significant sequela resulting from molecular mimicry to Campylobacter surface structures is the Guillain-Barré syndrome, which was mainly examined in the context of limited studies conducted in African populations. A dedicated subsection is allocated to the limited research on the veterinary medically important species Campylobacter fetus. There are significant differences in the composition of the gut microbiome, especially in rural areas, which affect the colonization with Campylobacter spp. and the manifestation of campylobacteriosis. There may be a problem of overdiagnosis due to asymptomatic colonization, particularly in the detection of Campylobacter using molecular biological techniques. To reduce the colonization and infection rate of Campylobacter, we propose implementing several control measures and urge further research to improve the current understanding of the peculiarities of campylobacteriosis in Africa.

4.
Antibiotics (Basel) ; 12(12)2023 Nov 28.
Article in English | MEDLINE | ID: mdl-38136703

ABSTRACT

Approximately half of the world's population is estimated to be infected with Helicobacter pylori [...].

5.
Antibiotics (Basel) ; 12(6)2023 May 26.
Article in English | MEDLINE | ID: mdl-37370288

ABSTRACT

Helicobacter pylori (H. pylori) infection is ubiquitous worldwide, with prevalence rates of greater than 70% in Africa. Symptomatic patients present with foregut gastrointestinal symptoms which can be readily diagnosed with standardized non-invasive or invasive tests. The biggest challenge, however, is in the management of this condition with rising antimicrobial resistance rates to most of the antibiotics recommended for therapy. This is a problem worldwide, but more specifically in Africa, where the socio-economic and political climate is such that eradication of this organism seems impossible. Furthermore, the recommended antimicrobial susceptibility testing for drug resistance is not widely available in Africa due to the lack of infrastructural as well as human resources. With the widespread unregulated use of antibiotics in some parts of Africa, the figures of antimicrobial resistance are likely to soar. In the face of these significant challenges, this 'perspectives' article aims to address the issue of antimicrobial resistance in Africa, by providing achievable and targeted goals to curb the spread of infection and rising antimicrobial resistance.

6.
Nat Rev Dis Primers ; 9(1): 19, 2023 04 20.
Article in English | MEDLINE | ID: mdl-37081005

ABSTRACT

Helicobacter pylori infection causes chronic gastritis, which can progress to severe gastroduodenal pathologies, including peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori is usually transmitted in childhood and persists for life if untreated. The infection affects around half of the population in the world but prevalence varies according to location and sanitation standards. H. pylori has unique properties to colonize gastric epithelium in an acidic environment. The pathophysiology of H. pylori infection is dependent on complex bacterial virulence mechanisms and their interaction with the host immune system and environmental factors, resulting in distinct gastritis phenotypes that determine possible progression to different gastroduodenal pathologies. The causative role of H. pylori infection in gastric cancer development presents the opportunity for preventive screen-and-treat strategies. Invasive, endoscopy-based and non-invasive methods, including breath, stool and serological tests, are used in the diagnosis of H. pylori infection. Their use depends on the specific individual patient history and local availability. H. pylori treatment consists of a strong acid suppressant in various combinations with antibiotics and/or bismuth. The dramatic increase in resistance to key antibiotics used in H. pylori eradication demands antibiotic susceptibility testing, surveillance of resistance and antibiotic stewardship.


Subject(s)
Gastritis , Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Humans , Helicobacter Infections/complications , Helicobacter Infections/epidemiology , Stomach Neoplasms/microbiology , Stomach Neoplasms/prevention & control , Gastritis/complications , Gastritis/diagnosis , Gastritis/epidemiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
7.
Res Vet Sci ; 152: 219-227, 2022 Dec 20.
Article in English | MEDLINE | ID: mdl-36007271

ABSTRACT

The high rate of antibiotic resistance constitutes a global threat to the continuous use of these drugs, because of increasing treatment failures. The aim of this study was to survey antibiotic prescription practices of veterinarians and the possible contribution to antimicrobial resistance (AMR) and antimicrobial stewardship (AMS) in Nigeria during the COVID era. This was a cross-sectional study that used a 33-question survey questionnaire administered to registered veterinarians in Nigeria. The study was both online survey and hard copy administered during the annual meeting of the veterinarians from July to October 2021. Descriptive statistics, bivariate analysis using Chi-square test were also done to analyze the results, while a two-tailed P-value of <0.05 at 95% confidence level was considered statistically significant. IBM SPSS Version 26 was used to analyze the data. A total of 172 respondents completed the online and hard copy questionnaire. Majority of the respondents engaged majorly in mixed veterinary practice (72.1%). A total of 53.5% were aware of the country's policy concerning antibiotic prescription, while majority (64.5%) do not do culture and sensitivity before antibiotic prescription. Majority (34.3%) felt that the risk of potential adverse drug reaction could affect their decision when choosing to prescribe an antibiotic to the owner. Majority (51.2%) felt that some antibiotics were over prescribed, while 26.7% opined that all antibiotics were appropriately prescribed. To improve antibiotic use and practice amongst veterinarians in Nigeria, dependence on laboratory services for antibiotic prescription, enforcement of national guidelines and monitoring of antibiotic prescription amongst the veterinarians is essential to curb over-prescription and strengthen antimicrobial stewardship.


Subject(s)
COVID-19 , Veterinarians , Animals , Humans , Nigeria/epidemiology , Anti-Bacterial Agents/therapeutic use , Cross-Sectional Studies , COVID-19/veterinary , Surveys and Questionnaires , Prescriptions
8.
Antibiotics (Basel) ; 9(5)2020 May 15.
Article in English | MEDLINE | ID: mdl-32429263

ABSTRACT

The medicinal plant Spathodea campanulata P. Beauv. (Bignoniaceae) has been traditionally applied for the prevention and treatment of diseases of the kidney and urinary system, the skin, the gastrointestinal tract, and inflammation in general. The present work shows for the first time how chemical components from this plant inhibit Helicobacter pylori growth by urease inhibition and modulation of virulence factors. The crude extract and the main fractions of S. campanulata bark were tested on H. pylori isolated strains and the active ones were further fractionated. Fractions and sub-fractions of the plant crude extract were characterized by ultra-high-performance liquid chromatographic tandem high resolution-mass spectrometry detection (UHPLC-HRMS). Several phenolics and triterpenoids were identified. Among the sub-fractions obtained, SB2 showed the capacity to inhibit H. pylori urease in a heterologous bacterial model. One additional sub-fraction (SE3) was able to simultaneously modulate the expression of two adhesins (HopZ and BabA) and one cytotoxin (CagA). The flavonol kaempferol was identified as the most interesting compound that deserves further investigation as a new hit for its capacity to modulate H. pylori virulence factors.

9.
BMC Res Notes ; 13(1): 258, 2020 May 26.
Article in English | MEDLINE | ID: mdl-32456668

ABSTRACT

OBJECTIVE: Nosocomial and community acquired multidrug resistant Klebsiella infections are wide spread resulting in high morbidity and mortality due to limited number of antibiotics treatment options. This study investigated efflux pump activity, biofilm forming potential and antibiotic susceptibility profile of Klebsiella spp. isolated from clinical samples in a tertiary hospital in Lagos Nigeria. Eighteen clinical Klebsiella spp. isolated from urine, blood and sputum were subjected to antibiotic susceptibility testing using the disc diffusion method. Efflux pump activity was evaluated by the ethidium bromide cartwheel method and biofilm forming ability was determined by the tissue culture plate technique. RESULTS: All 18 (100%) Klebsiella isolates were resistant to cefuroxime, cefixime, amoxicillin - clavulanate, ampicillin + cloxacillin, cefotaxime, and imipenem. Seventeen (94.4%) were resistant to ofloxacin while sixteen (88.9%) were resistance to nalidixic acid, Gentamicin and levofloxacin. All Klebsiella isolates possessed active efflux pump with the ability to form biofilm. However, their biofilm forming capabilities varied as 4 (22.2%) were strong, 3 (16.7%) were moderate and 11 (61.1%) were weak biofilm formers. Findings in this study reveal multiple factors at play in mediating the high level of antibiotic resistance observed in Klebsiella isolates. Hence a multifaceted approach is advocated in managing the infections caused by the pathogen.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Drug Resistance, Multiple, Bacterial , Klebsiella/drug effects , Amoxicillin/pharmacology , Ampicillin/pharmacology , Cefuroxime/pharmacology , Cells, Cultured , Community-Acquired Infections , Drug Combinations , Hospitals, Teaching , Hospitals, University , Humans , Imipenem/pharmacology , Klebsiella/isolation & purification , Klebsiella/metabolism , Klebsiella/pathogenicity , Klebsiella Infections/blood , Klebsiella Infections/drug therapy , Klebsiella Infections/urine , Microbial Sensitivity Tests , Nigeria , Ofloxacin/pharmacology , Tertiary Care Centers
10.
Eur J Microbiol Immunol (Bp) ; 9(2): 32-34, 2019 Jun 03.
Article in English | MEDLINE | ID: mdl-31223493

ABSTRACT

Campylobacter jejuni and Campylobacter coli are among the leading causes of gastroenteritis in humans worldwide, particularly in Africa. Poultry remains a major source of Campylobacter species and a vector of transmission to humans. This pilot study was aimed at isolating and determining the antibiotic susceptibility profiles of Campylobacter spp. from fresh poultry droppings collected from poultry farms in Lagos State, Nigeria. Susceptibility was assessed using the CLSI standards. Standard microbiological methods were used in isolation, identification, and characterization of Campylobacter spp. Isolates were subjected to antibiotic susceptibility testing by the disk diffusion method. Of the 150 poultry droppings analyzed, 8 (5.3%) harbored Campylobacter spp. All isolates proved to be C. coli since they were all negative for the hip gene. A percentage of 100% showed resistance to nalidixic acid, chloramphenicol, cloxacillin, and streptomycin. While 87.5% were susceptible to amoxicillin and amoxicillin/clavulanic acid, 62.5% were susceptible to tetracycline. Surprisingly, 62.5% of C. coli had decreased (intermediate) susceptibility to erythromycin. Although there was a low prevalence of C. coli from poultry in this study, the presence of antibiotic resistant strains circulating the food chain could result in treatment failures and difficulty in case management if involved in infections of humans.

11.
Infection ; 47(3): 351, 2019 06.
Article in English | MEDLINE | ID: mdl-30859453

ABSTRACT

The original version of this article unfortunately contained a mistake. In the introduction, the infectious dose of Vibrio cholerae was written as 103-108 instead of 103-108 cells.

12.
Minerva Gastroenterol Dietol ; 65(1): 36-41, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30293417

ABSTRACT

BACKGROUND: This multicenter study was undertaken to determine the prevalence of Helicobacter pylori (H. pylori) infection among dyspeptic patients with and without type 2 diabetes mellitus (T2DM). METHODS: Patients with dyspepsia were recruited from tertiary teaching hospitals, three in the South-West and one in the South-South regions of Nigeria, between November 2016 and August 2017. The participants had breath samples analyzed for H. pylori by the Urea Breath Test (UBT) following manufacturer's instructions. Dyspeptic patients who were diagnosed previously with T2DM were recorded. Crosstab using chi-square and correlation analyses were used to test (hypothesis) variables. RESULTS: The entire cohort included 471 dyspeptics, 19 (4%) of whom had T2DM. H. pylori infection was reported in 232/471 (49.3%) dyspeptics and 13/19 T2DM patients, without significant difference between diabetics and nondiabetics. The majority (84.6%) of those positive for UBT and T2DM were in the age group 52-71 years, while none was in the age group 72-91 years. There was no statistical significance (P>0.05) between the age group, UBT and T2DM positive. CONCLUSIONS: Our study showed that, in Nigeria, there is no difference in prevalence of H. pylori in dyspeptic patients with and without T2DM.


Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Dyspepsia/epidemiology , Helicobacter Infections/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Breath Tests , Child , Cohort Studies , Cross-Sectional Studies , Humans , Middle Aged , Nigeria/epidemiology , Prevalence , Young Adult
13.
Infection ; 47(3): 341-349, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30084058

ABSTRACT

BACKGROUND: Outbreaks of cholera in Africa seem to be unrelenting which has been continuous and recurrent leading to high morbidity and mortality in some quarters. OBJECTIVE: The objective of this narrative review is to investigate and identify factors responsible for the recurrent outbreaks of cholera in Africa and response strategies that have been employed in curbing the problem, with the view of aggregating otherwise sparing data needed for policy formulation geared towards control and eradication of the disease. METHODS: Search of literatures indexed in Google Scholar, PubMed and AJOL databases was carried out. Sixty-five eligible articles with reports on the risk factors that drive recurrent outbreaks, endemicity and response strategies were analyzed. RESULTS: Our findings indicate that continuous and recurrent outbreaks of cholera in Africa are fueled by cross-border migration, environmental reservoirs, socioeconomic factors, climate change and political instability. The review also identified specific response strategies and modelling approaches that have helped in containing and reducing the impact of these outbreaks. CONCLUSION: Paying attention and tackling these identified factors that are dependent and independent can help put an end to this running battle.


Subject(s)
Cholera/epidemiology , Cholera/prevention & control , Epidemics/prevention & control , Health Policy , Africa/epidemiology , Disease Outbreaks/prevention & control , Humans
14.
BMC Res Notes ; 11(1): 559, 2018 Aug 03.
Article in English | MEDLINE | ID: mdl-30075801

ABSTRACT

OBJECTIVES: Helicobacter pylori is a pathogenic bacterium that parasitizes the gastric mucous layer and the epithelial lining of the stomach causing duodenal ulcers, gastric ulcers and cardiovascular disease amongst others. This study aimed at establishing the epidemiologic profile of H. pylori infection in gastritis patients presenting at the Melong District Hospital. RESULTS: Blood, stool and epidemiological data collected from 500 patients were analyzed for the presence of H. pylori antibody in serum, antigen in stool and elucidation of risk factors captured in questionnaires. Of 500 blood samples, 217 (43.4%) were seropositive with male and female seroprevalences of 45.5% (61/134) and 42.6% (156/366) respectively. Similarly, 47.4% (237/500) samples tested positive for stool antigen with prevalences of 47.0% (63/134) for males and 47.5% (174/366) for females. The antigen prevalence was higher (53.2%; 118/222) in older patients (> 50 years) than in younger patients (42.8%; 119/278; P = 0.021). The antigen test had a higher (47.4%) prevalence than the antibody test (43.4%). Educational level, source of income, source of drinking water, age of patients, and alcohol consumption had positive associations with H. pylori infection. These results have clinical and epidemiological significance and call for intervention to mitigate the situation.


Subject(s)
Gastritis/microbiology , Helicobacter Infections/epidemiology , Helicobacter pylori/isolation & purification , Cameroon , Female , Gastritis/complications , Helicobacter Infections/complications , Humans , Male , Middle Aged , Prevalence , Risk Factors
15.
J Glob Antimicrob Resist ; 13: 143-145, 2018 06.
Article in English | MEDLINE | ID: mdl-29355664

ABSTRACT

OBJECTIVES: The aim of this study was to determine the occurrence of 16S rRNA mutations associated with low-level tetracycline resistance in Helicobacter pylori isolates from adult dyspeptic patients in South West Nigeria. METHODS: Susceptibility testing to tetracycline of 50 H. pylori isolates was performed by Etest. The 535-bp conserved region of the H. pylori tetracycline-binding site of 16S rRNA was amplified by PCR, followed by sequencing and multiple sequence alignment for all 50 clinical isolates. RESULTS: Of the 50 clinical isolates examined, DNA sequence analysis revealed nucleotide substitutions in 7 isolates at positions 926-928. Of the seven isolates, two demonstrated reduced susceptibility to tetracycline with Etest minimum inhibitory concentrations (MICs) of 0.75-1.0mg/L, whilst the other five isolates were resistant with MICs of 1.5-24mg/L (resistance breakpoint >1mg/L). The two isolates with reduced susceptibility had single nucleotide substitution of A926G, whilst the five resistant isolates demonstrated double base pair substitutions of G927T/A928C and A926G/A928C and a single nucleotide substitution of A926G. CONCLUSIONS: This study shows that low-level tetracycline resistance amongst H. pylori-positive dyspeptic patients is associated with reduced susceptibility and resistance to tetracycline. This is the result of 1-bp and 2-bp differences in positions 926 and 926-928, respectively, in the 16S rRNA of H. pylori.


Subject(s)
Dyspepsia/microbiology , Helicobacter pylori/drug effects , Tetracycline Resistance/genetics , Tetracycline/pharmacology , Anti-Bacterial Agents , Biopsy , DNA, Bacterial/genetics , Dyspepsia/epidemiology , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Helicobacter Infections/microbiology , Helicobacter pylori/isolation & purification , Humans , Microbial Sensitivity Tests , Mutation , Nigeria/epidemiology , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Stomach/microbiology , Stomach/pathology , Tetracycline/therapeutic use
16.
Minerva Gastroenterol Dietol ; 64(3): 222-234, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29327819

ABSTRACT

Helicobacter pylori (H. pylori) relationship with humans is believed to have originated in Africa and three African H. pylori populations have been identified: hpAfrica1, hpAfrica2 and hpNEAfrica. Actually, H. pylori infection is a ubiquitous infection in developing countries, particularly Africa. In this continent, the prevalence of H. pylori is higher and the bacterium is acquired at an early age compared to developed countries. In fact, while it affects over 50% of humans in developed countries its prevalence reaches 80% or more among adults in Africa. This paper reviews works in literatures, including epidemiology, virulence genes, gastric pathology and antimicrobial treatment and resistance of H. pylori in Africa.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Africa/epidemiology , Drug Resistance, Bacterial , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Helicobacter pylori/drug effects , Helicobacter pylori/genetics , Helicobacter pylori/pathogenicity , Humans , Prevalence , Stomach Neoplasms/microbiology
17.
PLoS One ; 12(5): e0176454, 2017.
Article in English | MEDLINE | ID: mdl-28463973

ABSTRACT

Antibiotic resistance in Helicobacter pylori is a factor preventing its successful eradication. Particularly in developing countries, resistance against commonly used antibiotics is widespread. Here, we present an epidemiological study from Nigeria with 111 isolates. We analyzed the associated disease outcome, and performed a detailed characterization of these isolated strains with respect to their antibiotic susceptibility and their virulence characteristics. Furthermore, statistical analysis was performed on microbiological data as well as patient information and the results of the gastroenterological examination. We found that the variability concerning the production of virulence factors between strains was minimal, with 96.4% of isolates being CagA-positive and 92.8% producing detectable VacA levels. In addition, high frequency of bacterial resistance was observed for metronidazole (99.1%), followed by amoxicillin (33.3%), clarithromycin (14.4%) and tetracycline (4.5%). In conclusion, this study indicated that the infection rate of H. pylori infection within the cohort in the present study was surprisingly low (36.6%). Furthermore, an average gastric pathology was observed by histological grading and bacterial isolates showed a uniform pathogenicity profile while indicating divergent antibiotic resistance rates.


Subject(s)
Helicobacter pylori/drug effects , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Antigens, Bacterial/metabolism , Bacterial Proteins/metabolism , Blotting, Western , Child , Child, Preschool , Drug Resistance, Bacterial/genetics , Female , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Helicobacter Infections/microbiology , Helicobacter pylori/genetics , Helicobacter pylori/pathogenicity , Humans , Infant , Male , Microbial Sensitivity Tests , Middle Aged , Multilocus Sequence Typing , Nigeria/epidemiology , Phylogeny , Urease/metabolism , Young Adult
19.
Nat Microbiol ; 2: 16188, 2016 10 17.
Article in English | MEDLINE | ID: mdl-27748756

ABSTRACT

Helicobacter pylori (Hp) strains that carry the cag type IV secretion system (cag-T4SS) to inject the cytotoxin-associated antigen A (CagA) into host cells are associated with peptic ulcer disease and gastric adenocarcinoma. CagA translocation by Hp is mediated by ß1 integrin interaction of the cag-T4SS. However, other cellular receptors or bacterial outer membrane adhesins essential for this process are unknown. Here, we identify the HopQ protein as a genuine Hp adhesin, exploiting defined members of the carcinoembryonic antigen-related cell adhesion molecule family (CEACAMs) as host cell receptors. HopQ binds the amino-terminal IgV-like domain of human CEACAM1, CEACAM3, CEACAM5 or CEACAM6 proteins, thereby enabling translocation of the major pathogenicity factor CagA into host cells. The HopQ-CEACAM interaction is characterized by a remarkably high affinity (KD from 23 to 268 nM), which is independent of CEACAM glycosylation, identifying CEACAMs as bona fide protein receptors for Hp. Our data suggest that the HopQ-CEACAM interaction contributes to gastric colonization or Hp-induced pathologies, although the precise role and functional consequences of this interaction in vivo remain to be determined.


Subject(s)
Adhesins, Bacterial/metabolism , Antigens, Bacterial/metabolism , Bacterial Adhesion , Bacterial Proteins/metabolism , Cell Adhesion Molecules/metabolism , Helicobacter pylori/physiology , Host-Pathogen Interactions , Protein Transport , Cell Line , Humans , Protein Binding
20.
BMC Genomics ; 15: 310, 2014 Apr 27.
Article in English | MEDLINE | ID: mdl-24767410

ABSTRACT

BACKGROUND: The human gastric pathogen Helicobacter pylori is a paradigm for chronic bacterial infections. Its persistence in the stomach mucosa is facilitated by several mechanisms of immune evasion and immune modulation, but also by an unusual genetic variability which might account for the capability to adapt to changing environmental conditions during long-term colonization. This variability is reflected by the fact that almost each infected individual is colonized by a genetically unique strain. Strain-specific genes are dispersed throughout the genome, but clusters of genes organized as genomic islands may also collectively be present or absent. RESULTS: We have comparatively analysed such clusters, which are commonly termed plasticity zones, in a high number of H. pylori strains of varying geographical origin. We show that these regions contain fixed gene sets, rather than being true regions of genome plasticity, but two different types and several subtypes with partly diverging gene content can be distinguished. Their genetic diversity is incongruent with variations in the rest of the genome, suggesting that they are subject to horizontal gene transfer within H. pylori populations. We identified 40 distinct integration sites in 45 genome sequences, with a conserved heptanucleotide motif that seems to be the minimal requirement for integration. CONCLUSIONS: The significant number of possible integration sites, together with the requirement for a short conserved integration motif and the high level of gene conservation, indicates that these elements are best described as integrating conjugative elements (ICEs) with an intermediate integration site specificity.


Subject(s)
Helicobacter pylori/physiology , Gene Transfer, Horizontal , Genes, Bacterial , Geography , Helicobacter pylori/classification , Helicobacter pylori/genetics , Molecular Sequence Data , Phylogeny
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