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Hospital environmental surfaces are potential reservoirs for transmitting hospital-associated pathogens. This study aimed to profile microbiomes and antibiotic resistance genes (ARGs) from hospital environmental surfaces using 16S rRNA amplicon and metagenomic sequencing at a tertiary teaching hospital in Malaysia. Samples were collected from patient sinks and healthcare staff counters at surgery and orthopaedic wards. The samples' DNA were subjected to 16S rRNA amplicon and shotgun sequencing to identify bacterial taxonomic profiles, antibiotic resistance genes, and virulence factor pathways. The bacterial richness was more diverse in the samples collected from patient sinks than those collected from staff counters. Proteobacteria and Verrucomicrobia dominated at the phylum level, while Bacillus, Staphylococcus, Pseudomonas, and Acinetobacter dominated at the genus level. Staphylococcus epidermidis and Staphylococcus aureus were prevalent on sinks while Bacillus cereus dominated the counter samples. The highest counts of ARGs to beta-lactam were detected, followed by ARGs against fosfomycin and cephalosporin. We report the detection of mcr-10.1 that confers resistance to colistin at a hospital setting in Malaysia. The virulence gene pathways that aid in antibiotic resistance gene transfer between bacteria were identified. Environmental surfaces serve as potential reservoirs for nosocomial infections and require mitigation strategies to control the spread of antibiotic resistance bacteria.
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BACKGROUND: The emergence of multidrug-resistant Helicobacter pylori has undermined eradication strategies to prevent the development of gastric cancer. This study was conducted to estimate the prevalence of secondary antibiotic resistance of H. pylori in urban multicultural areas in Malaysia. METHODS: From January 2017 to December 2021, gastric biopsies from 218 patients with a history of H. pylori eradication failure were sent to our laboratory for antibiotic susceptibility testing. A minimal inhibitory concentration was determined for six antibiotics, namely metronidazole, clarithromycin, levofloxacin, amoxicillin, tetracycline, and rifampicin using the E-test method. Two multidrug-resistant H. pylori strains identified in this study were subjected to whole genome sequencing. RESULTS: Eradication failure was observed to be significantly higher in the Malaysian Chinese patients than in the Malaysian Indian and Malay patients. H. pylori were successfully isolated from 51 patients (23.4%). Overall, the antibiotic resistance rates of H. pylori to metronidazole, clarithromycin, levofloxacin, and amoxicillin were 82.4% (42/51), 72.5% (37/51), 52.9% (27/51), and 3.9% (2/51), respectively. Resistance to tetracycline and rifampicin were not observed during the study period. Resistance to more than one antibiotic was observed in 82.4% (42/51) of the isolates, of which 42.2% (19/42) were resistant to three antibiotic classes. Resistance to both clarithromycin and metronidazole were most frequently observed in isolates with dual resistance (56.5%; 13/23). Codon substitutions in penicillin-binding protein 1A (V346L, V374L, G595_V596InsG, Y604H, and N608S) were detected in amoxicillin-resistance H. pylori strains. Herein, we report amoxicillin resistance in H. pylori isolated from Malaysian patients, and its resistance mechanism, for the first time. CONCLUSION: Our results show the increase trend in secondary multidrug resistance in H. pylori isolates, which warrants continuous surveillance.
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Despite the fact that the incidence of gastric cancer has declined over the last decade, it is still the world's leading cause of cancer-related death. The diagnosis of early gastric cancer is difficult, as symptoms of this cancer only manifest at a late stage of cancer progression. Thus, the prognosis of gastric cancer is poor, and the current treatment for improving patients' outcomes involves the application of surgery and chemotherapy. Immunotherapy is one of the most recent therapies for gastric cancer, whereby the immune system of the host is programmed to combat cancer cells, and the therapy differs based upon the patient's immune system. However, an understanding of the role of immune cells, namely the cell-mediated immune response and the humoral immune response, is pertinent for applications of immunotherapy. The roles of immune cells in the prognosis of gastric cancer have yielded conflicting results. This review discusses the roles of immune cells in gastric cancer pathogenesis, specifically, T cells, B cells, macrophages, natural killer cells, and dendritic cells, as well as the evidence presented thus far. Understanding how cancer cells interact with immune cells is of paramount importance in designing treatment options for gastric cancer immunotherapy.
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BACKGROUND: Expression of cluster of differentiation (CD) antigens changes according to disease status and inflammation. Profiles of CD antigens expression in gastric cancer patients are different based on the status of H. pylori infection. AIMS: We conducted this study to profile CD antigen markers in gastric adenocarcinoma cells (AGS cell line) infected with distinct cytotoxin-associated gene A (cagA) genotypes of H. pylori clinical isolates. METHODS: The AGS cells were infected with H. pylori isolates with different cagA genotypes, and CD antigens expression was determined using DotScan™ antibody microarray. Formation of "hummingbird" phenotype was determined, and the percentage was calculated. RESULTS: H. pylori strains harboring cagA upregulated the expression of CD antigen involved in cancer stem cell formation (CD55), but downregulated CD antigens involved in immune regulation (CD40 and CD186) and cell adhesion (CD44). CD54 (neutrophil adhesion) and CD71 (iron transfer) were highly downregulated in the gastric cells infected with Western cagA isolates compared with East Asian isolates. CD antigen expression was different in the cells infected with H. pylori harboring different CagA EPIYA (Glu-Pro-Ile-Tyr-Ala) numbers, in which higher repression of CD54 and CD15 (Lewis x antigen) were observed in the isolate with the highest number of EPIYA motif. Furthermore, higher downregulation of CD15 was observed in the infected gastric cells with high percentage of "hummingbird" phenotype than that of low percentage of "hummingbird" phenotype. CONCLUSION: Our study demonstrated the critical roles of CD antigens in the CagA pathogenesis and should be investigated further.
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Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Motivos de Aminoácidos , Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Antígenos CD/metabolismo , Antígenos de Superfície , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Carcinogênese , Citotoxinas/metabolismo , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Humanos , Ferro/metabolismo , Antígenos CD15/metabolismoRESUMO
The major challenges that delay the implementation of pharmacogenomics based clinical practice in the developing countries, primarily the low- and middle-income countries need to be recognized. This review was conducted to systematically review evidence of the cost-effectiveness for the conduct of pharmacogenomics testing in the developing countries. Studies that evaluated the cost-effectiveness of pharmacogenomics testing in the developing countries as defined by the United Nations were included in this study. Twenty-seven articles met the criteria. Pharmacogenomics effectiveness were evaluated for drugs used in the treatment of cancers, cardiovascular diseases and severe cutaneous adverse reactions in gout and epilepsy. Most studies had reported pharmacogenomics testing to be cost-effective (cancers, cardiovascular diseases, and tuberculosis) and economic models were evaluated from multiple perspectives, different cost categories and time horizons. Additionally, most studies used a single gene, rather than a gene panel for the pharmacogenomics testing. Genotyping cost and frequency of risk alleles in the populations influence the cost-effectiveness outcome. Further studies are warranted to examine the clinical and economic validity of pharmacogenomics testing in the developing countries.
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Doenças Cardiovasculares , Farmacogenética , Análise Custo-Benefício , Países em Desenvolvimento , Humanos , Testes FarmacogenômicosRESUMO
Orang Asli are the oldest inhabitants in Peninsular Malaysia that forms as a national minority while the Malays are the majority. The study aimed to screen the mitochondrial genomes of the Orang Asli and the Malays to discover the disease-associated variants. A total of 99 Orang Asli from six tribes (Bateq, Cheq Wong, Orang Kanaq, Kensiu, Lanoh, and Semai) were recruited. Mitochondrial genome sequencing was conducted using a next-generation sequencing platform. Furthermore, we retrieved mitochondrial DNA sequences from the Malays for comparison. The clinical significance, pathogenicity prediction and frequency of variants were determined using online tools. Variants associated with mitochondrial diseases were detected in the 2 populations. A high frequency of variants associated with mitochondrial diseases, breast cancer, prostate cancer, and cervical cancer were detected in the Orang Asli and modern Malays. As medicine evolves to adopt prediction and prevention of diseases, this study highlights the need for intervention to adopt genomics medicine to strategise better healthcare management as a way forward for Precision Health.
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Sinalização do Cálcio/genética , Variação Genética , Genoma Humano , Genoma Mitocondrial , Sudeste Asiático , Cálcio/metabolismo , HumanosRESUMO
Infection with Helicobacter pylori is associated with the development of gastric cancer. Although the prevalence of gastric cancer has declined throughout years due to improvement in early screening strategy, mortality due to gastric cancer has not changed. Incidence and mortality due to gastric cancer are higher in developing countries as compared to developed countries. Diagnosis and prognosis of gastric cancer are still poor with patients usually diagnosed with cancer at an advanced stage. Eradication of H. pylori is pertinent for the prevention of gastric cancer. However, the rise in antimicrobial resistance among H. pylori isolates has complicated the prevention strategy. H. pylori express multiple virulence factors for survival in the hostile acid gastric environment. The expression of oncogenic protein cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA), and outer inflammatory protein is essential for H. pylori to exert pathogenesis towards the host. Interestingly, <3% of H. pylori-infected subjects develop gastric cancer, suggesting a unique way of interaction between the host's immune response and H. pylori virulence factors. This article is aimed to review the epidemiology and role of H. pylori in gastric carcinogenesis. A better understanding of the interaction between H. pylori virulence factors and host is required for better gastric cancer prevention.
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Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/imunologia , Fatores de Virulência/imunologia , Virulência/imunologia , Carcinogênese/imunologia , Humanos , Prognóstico , Neoplasias Gástricas/microbiologiaRESUMO
BACKGROUND: Comprehensive immunophenotyping cluster of differentiation (CD) antigens in gastric adenocarcinoma, specifically between Helicobacter pylori-infected and -uninfected gastric cancer patients by using DotScan(™) antibody microarray has not been conducted. Current immunophenotyping techniques include flow cytometry and immunohistochemistry are limited to the use of few antibodies for parallel examination. We used DotScan(™) antibody microarray consisting 144 CD antibodies to determine the distribution of CD antigens in gastric adenocarcinoma cells and to elucidate the effect of H. pylori infection toward CD antigen expression in gastric cancer. METHODS: Mixed leukocytes population derived from gastric adenocarcinoma patients were immunophenotyped using DotScan(™) antibody microarray. AGS cells were infected with H. pylori strains and cells were captured on DotScan(™) slides. RESULTS: Cluster of differentiation antigens involved in perpetuating the tolerance of immune cells to tumor cells was upregulated in gastric adenocarcinoma cells compared to normal cells. CD279 which is essential in T cells apoptosis was found to be upregulated in normal cells. Remarkably, H. pylori-infected gastric cancer patients exhibited upregulated expression of CD27 that important in maintenance of T cells. Infection of cagA+ H. pylori with AGS cells increased CD antigens expression which involved in cancer stem cell while cagA- H. pylori polarized AGS cells to express immune-regulatory CD antigens. Increased CD antigens expression in AGS cells infected with cagA+ H. pylori were also detected in H. pylori-infected gastric cancer patients. CONCLUSION: This study suggests the tolerance of immune system toward tumor cells in gastric cancer and distinct mechanisms of immune responses exploited by different H. pylori strains.