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Machine learning and bioinformatics to identify biomarkers in response to burkholderia pseudomallei infection in mice

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BIOCELL 2024年第4期48卷 613-621页

作者： YAO FANG FEI XIA FEIFEI TIAN L EI QU FANG YANG JUAN FANG ZHENHONG HU HAICHAO LIU Department of Respiratory and Critical Care Medicine General Hospital of Center Theater of PLAWuhan430070China School of Medicine Wuhan University of Science and TechnologyWuhan430065China School of Life Science and Engineering Southwest Jiaotong UniversityChengdu611756China

Objective:In the realm of Class I pathogens,burkholderia pseudomallei(BP)stands out for its propensity to induce severe pathogenicity.Investigating the intricate interactions between BP and host cells is imperative for comprehending the dynamics of BP infection and discerning biomarkers indicative of the host cell response process.Methods:mRNA extraction from BP-infected mouse macrophages constituted the initial step of our study.Employing gene expression arrays,the extracted RNA underwent conversion into digital signals.The percentile shift method facilitated data processing,with the identiﬁcation of genes manifesting signiﬁcant differences accomplished through the application of the t-test.Subsequently,a comprehensive analysis involving Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway was conducted on the differentially expressed genes(DEGs).Leveraging the ESTIMATE algorithm,gene signatures were utilized to compute risk scores for gene expression data.Support vector machine analysis and gene enrichment scores were instrumental in establishing correlations between biomarkers and macrophages,followed by an evaluation of the predictive power of the identiﬁed biomarkers.Results:The functional and pathway associations of the DEGs predominantly centered around G protein-coupled receptors.A noteworthy positive correlation emerged between the blue module,consisting of 416 genes,and the StromaScore.FZD4,identiﬁed through support vector machine analysis among intersecting genes,indicated a robust interaction with macrophages,suggesting its potential as a robust biomarker.FZD4 exhibited commendable predictive efﬁcacy,with BP infection inducing its expression in both macrophages and mouse lung tissue.Western blotting in macrophages conﬁrmed a signiﬁcant upregulation of FZD4 expression from 0.5 to 24 h post-infection.In mouse lung tissue,FZD4 manifested higher expression in the cytoplasm of pulmonary epithelial cells in BP-infected lungs than in the control group.Conclusion:Theseﬁndings underscor

关键词： burkholderia pseudomallei Microarray assay Machine learning Bioinformatics FZD4

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Biofilm analyses and exoproduct release by clinical and environmental isolates of burkholderia pseudomallei from Brazil

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Asian Pacific Journal of Tropical Medicine 2023年第7期16卷 321-328页

作者： Glaucia Morgana de Melo Guedes Crister JoséOcadaque Alyne Soares Freitas Rodrigo Machado Pinheiro Giovanna Barbosa Riello Silviane Praciano Bandeira Rossana de Aguiar Cordeiro Marcos Fábio Gadelha Rocha JoséJúlio Costa Sidrim Débora de Souza Collares Maia Castelo-Branco Department of Pathology and Legal Medicine Postgraduate Program in Medical MicrobiologyGroup of Applied Medical MicrobiologyFederal University of CearáFortalezaCEBrazil Department of Clinical and Toxicological Analysis School of PharmacyFederal University of CearáFortalezaCEBrazil Department of Pathology and Legal Medicine Postgraduate Program in Medical MicrobiologyLaboratory of Emerging and Reemerging PathogensFederal University of CearáFortalezaCEBrazil School of Veterinary Medicine Postgraduate Program in Veterinary SciencesState University of CearáFortalezaCEBrazil

Objective:To characterize biofilm production by clinical(n=21)and environmental(n=11)isolates of burkholderia pseudomallei and evaluate the production of proteases,hemolysins and siderophores.Methods:Initially,the 32 strains were evaluated for biofilm production in Müller-Hinton broth-1%glucose(MH-1%glucose)and BHI broth-1%glucose,using the crystal violet staining technique.Subsequently,growing(48 h)and mature(72 h)biofilms were evaluated by confocal microscopy.Finally,the production of proteases,hemolysins and siderophores by planktonic aggregates,growing biofilms and mature biofilms was evaluated.Results:All isolates produced biofilms,but clinical isolates had significantly higher biomass in both MH-1%glucose(Pburkholderia pseudomallei biofilms.

关键词： Mangosteen burkholderia pseudomallei Biofilms Proteases Hemolysins Siderophores

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T6SS-5 and the cGAS-STING pathway in burkholderia pseudomallei infection and immunity

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Asian Pacific Journal of Tropical Biomedicine 2023年第3期13卷 94-103页

作者： Noreafifah Semail Nik Mohd Noor Nik Zuraina Yasmin Khairani Muhammad Ismadi Nurul Iman Mohamad Azian Harun Ismail Aziah Zakuan Zainy Deris Department of Medical Microbiology and Parasitology School of Medical SciencesUniversiti Sains Malaysia16150 Kubang KerianKelantanMalaysia School of Biology Faculty of Applied ScienceUniversiti Teknologi MaraShah Alam40450 SelangorMalaysia Institute for Research in Molecular Medicine Universiti Sains Malaysia16150 Kubang KerianKelantanMalaysia

burkholderia pseudomallei is a causative agent of melioidosis that can infect humans and animals in endemic countries,specifically in Southeast Asia and tropical Australia.A fundamental component for the pathogenesis of burkholderia pseudomallei is the capability of the bacterium to enter,survive,replicate,and cause disease in a host cell by inducing the host cell fusion.Cell fusion results in multinucleated-giant cell formation,thus enabling the dissemination of burkholderia pseudomallei intracellularly.cGAS reacts to burkholderia pseudomallei infection by activating the cGAS-STING pathway and subsequently limiting host's aberrant cell division and cellular replication by inducing autophagic cell death.In this review,we discuss the host-pathogen interactions between the typeⅥsecretion system 5(T6SS-5)of burkholderia pseudomallei and human cGAS pathway in melioidosis infections.Since T6SS-5 is a main virulent factor in burkholderia pseudomallei and the c GAS pathway is vital for host immune response,elucidating their functions is important for better understanding the pathogenesis of burkholderia pseudomallei.

关键词： burkholderia pseudomallei Melioidosis T6SS-5 c GAS-STING IFN-1

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Fatal hemophagocytic lymphohistiocytosis-induced multiorgan dysfunction secondary to burkholderia pseudomallei sepsis: A case report

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World Journal of Clinical Cases 2023年第30期11卷 7372-7379页

作者： Ming-Ze Sui Ke-Cheng Wan Yuan-Lu Chen Huan-Long Li Shan-Shan Wang Ze-Fu Chen Department of Pulmonary and Critical Care Medicine Kunming Children’s HospitalYunnan Key Laboratory of Children’s Major Disease ResearchKunming 650034Yunnan ProvinceChina Department of Pediatrics Hainan General HospitalHaikou 570311Hainan ProvinceChina

BACKGROUND burkholderia pseudomallei(B.pseudomallei)is a short,straight,medium-sized Gramnegative bacterium that mostly exists alone,without a capsule or spores,has more than three flagella at one end,and actively moves.B.pseudomallei confers high morbidity and mortality,with frequent granulocytopenia in B.pseudomallei sepsisrelated deaths.However,mortality may be related to hemophagocytic lymphohistiocytosis(HLH)secondary to B.pseudomallei infection.CASE SUMMARY A 12-year-old female was referred from a local hospital to the pediatric intensive care unit with suspected septic shock and fever,cough,dyspnea,and malaise.After admission,supportive symptomatic treatments including fluid resuscitation,anti-infective therapy,mechanical ventilation,and a vasoactive drug maintenance cycle were carefully initiated.The patient became unconscious,her blood pressure could not be maintained even under the exposure of vasoactive drugs,and she experienced cardiorespiratory arrest.The patient died due to ineffective high-quality in-hospital cardiopulmonary resuscitation.A subsequent bone marrow smear examination revealed extensive phagocytosis,and the blood culture was positive for B.pseudomallei.Family history revealed a sibling death from B.pseudomallei sepsis 5 years earlier.CONCLUSION The higher mortality rate in patients with B.pseudomallei sepsis may be related to secondary HLH after infection,wherein multiorgan dysfunction syndrome may be directly related to infection or immune damage caused by secondary HLH.Patients with B.pseudomallei can be asymptomatic and can become an infective source.

关键词： burkholderia pseudomallei Sepsis Septic shock Hemophagocytic lymphohistiocytosis Asymptomatic carrier Case report

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A Case on Acute burkholderia pseudomallei Pericarditis

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Chinese Medical Journal 2016年第18期129卷 2256-2257页

作者： Xing-Jun Cai Yi-Jiang Huang Yi-Hui Fu Department of Respiratory Hainan General Hospital Haikou Hainan 570311 China

Melioidosis is an endemic communicable disease caused by burkholderia pseudomallei and a prevalent amphixenosis in tropical and subtropical regions. The main routes of infection are thought to be through compromised surface tissues and through inhalation of contaminated soil and water. B. pseudomallei can affect all organs, but pulmonary infection is the most common symptom, which could easily lead to sepsisYl Here, we reported what we believe is a rare case of acute pericarditis caused by B. pseudomallei infection.

关键词： burkholderia pseudomallei Melioidosis Pericarditis Tuberculosis

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Clinical and environmental isolates of burkholderia pseudomallei from Brazil: Genotyping and detection of virulence gene

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Asian Pacific Journal of Tropical Medicine 2017年第10期10卷 945-951页

作者： Tereza de Jesus Pinheiro Gomes Bandeira Debora de Souza Collares Maia Castelo-Branco Marcos Fabio Gadelha Rocha Rossana de Aguiar Cordeiro Crister Jose Ocadaque Manoel de Araújo Neto Paiva Raimunda Samia Nogueira Brilhante Jose Júlio Costa Sidrim Specialized Medical Mycology Center Postgraduate Program in Medical Microbiology Federal University of Ceará Christus School of Medicine Postgraduate Program in Veterinary Sciences State University of Ceará Federal Institute of Education Science and Technology of Ceará

Objective: To evaluate the genetic diversity of clinical and environmental isolates of burkholderia pseudomallei(B.pseudomallei) recovered in Ceara, Brazil, and screen these isolates for the presence of type three secretion system virulence gene.Methods: Nineteen B.pseudomallei isolates(9 from clinical cases and 10 from soils)were analyzed.Random amplified polymorphic DNA was performed with primers OPQ-2, OPQ-4 and OPQ-16 to evaluate the genetic diversity, and type three secretion system gene was detected through polymerase chain reaction.Results: Random amplified polymorphic DNA showed a genetic relatedness of approximately 50% among the tested B.pseudomallei isolates, which were grouped into two clades, of which the biggest ones comprised 18/19 isolates for primer OPQ-2, and 17/19 isolates for primer OPQ-16.Primer OPQ-4 grouped the isolates into three clades comprising 1/19, 3/19 and 15/19 isolates.Additionally, type three secretion system gene was detected in all tested isolates.Conclusions: This is an effort to type B.pseudomallei strains from Ceara, which is important for better understanding this pathogen, contributing for the epidemiological surveillance of melioidosis in this endemic region.

关键词： burkholderia pseudomallei Melioidosis RAPD TTSS 基因

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Multi-systemic melioidosis in a patient with type 2 diabetes in nonendemic areas:A case report and review of literature

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World Journal of Clinical Cases 2024年第9期12卷 1669-1676页

作者： Huan-Yu Ni Ying Zhang Dong-Hai Huang Feng Zhou Department of Endocrinology Puren HospitalWuhan University of Science and TechnologyWuhan 430080Hubei ProvinceChina School of Medicine Wuhan University of Science and TechnologyWuhan 430080Hubei ProvinceChina Department of Critical Care Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071Hubei ProvinceChina Department of Rheumatology and Immunology Puren HospitalWuhan University of Science and TechnologyWuhan 430080Hubei ProvinceChina

BACKGROUND Melioidosis,an infectious disease caused by burkholderia pseudomallei(B.pseudomallei),occurs endemically in Southeast Asia and Northern Australia and is a serious opportunistic infection associated with a high mortality rate.CASE SUMMARY A 58-year-old woman presented with scattered erythema on the skin of her limbs,followed by fever and seizures.B.pseudomallei was isolated successively from the patient’s urine,blood,and pus.Magnetic resonance imaging showed abscess formation involving the right forehead and the right frontal region.Subsequently,abscess resection and drainage were performed.The patient showed no signs of relapse after 4 months of follow-up visits post-treatment.CONCLUSION We present here a unique case of multi-systemic melioidosis that occurs in nonendemic regions in a patient who had no recent travel history.Hence,it is critical to enhance awareness of melioidosis in non-endemic regions.

关键词： Melioidosis burkholderia pseudomallei Endemic Diabetes Case report

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Melioidosis an Imported Infection in Qatar: Case Series and Literature Review

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Advances in Infectious Diseases 2022年第2期12卷 175-192页

作者： Mohammed Abu Khattab Mohamed Abou Kamar Adham Darweesh Anand Deshmukh Infectious Disease Division Department of Medicine Hamad General Hospital Doha Qatar Radiology Department Hamad General Hospital Doha Qatar Microbiology Department University Hospital Coventry and Warwickshire NHS Trust Coventry UK

Introduction: Melioidosis is a tropical infectious disease caused by Gramnegative bacteria burkholderia pseudomallei (B. pseudomallei). This soil-borne disease is endemic in Southeast Asia and Northern Australia. In our country it was reported once before in 2000 in a patient who presented with subdural empyema. Case Series Report: We are reporting six cases of Melioidosis presented to our hospital in very close time with different clinical presentations. All patients were from Indian subcontinent. In 3 cases we treated with Meropenem plus Trimethoprim-Sulfamethoxazole (TMP-SMX) followed by oral TMP-SMX and Doxycycline for around 6 months with good clinical and radiological response, while the fourth case was treated with oral TMP-SMX and Doxycycline for 1 month but he lost to follow up, the Fifth cases were treated with IV Ceftazidime followed by TMP-SMX and Doxycycline for 9 weeks, the Sixth cases were treated with IV Ceftazidime followed by TMP-SMX and Amoxicillin/Clavulanic acid for 20 days, there was no mortality reported in our case series for both types Bactraemic and Abactraemic Melioidosis. Conclusions: This case series highlights the importance of early identification of B. pseudomallei which requires a high index of clinical suspicion as well as good understanding of demographical and travel history. Microbiological identification of B. pseudomallei is essential and requires notification of the microbiologist for suspicion of that infection. Prolonged antimicrobial therapy is required for a better clinical outcome.

关键词： Melioidosis Bactraemic Abactraemic Melioidosis burkholderia pseudomallei Infection

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Melioidosis in India and Bangladesh: A review of case reports

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Asian Pacific Journal of Tropical Medicine 2018年第5期11卷 320-329页

作者： Meghan Tipre Paul Vijay Kingsley Tamika Smith Mark Leader Nalini Sathiakumar Department of Epidemiology School of Public HealthUniversity of Alabama Pantai Hospital Ipoh

Objective: To conduct an epidemiological and clinical review of published case reports of melioidosis from India and Bangladesh. Methods: Data from published case reports were abstracted and summarized. We further compared the clinical epidemiology of the melioidosis cases in India with case series from highly endemic areas in Northern Australia and Southeast Asia to elucidate any differences in presentations and risk factors between the regions.Results: We identified a total of 99 cases published between 1953 and June 2016, originating from India(n=85) or Bangladesh(n=14). Cases were predominantly male and ranged in age from 1 month to 90 years. Diabetes mellitus was the most common risk factor reported(58%). About 28% of the cases had history of exposure via high-risk occupations or exposure to contaminated water. The overall case fatality rate(CFR) was 26%. Factors influencing mortality included the occurrence of septic shock(CFR, 80%), environmental exposure(CFR,39%), primary presentation of pneumonia(CFR, 38%), misdiagnosed and/or mistreated cases(CFR, 33%) or the presence of a risk factor(CFR, 29%). Because of the small number of cases in Bangladesh, pattern of clinical epidemiology is limited to India. Soft tissue abscess(37%)was the most common clinical presentation reported from India followed by pneumonia(24%)and osteomyelitis/septic arthritis(18%). Neurological melioidosis(n=10, 12%) presented as pyemic lesions of the brain or meninges. A few cases of prostatic abscess(n=4) in men and parotid abscess(n=4) were also noted. The above patterns were consistent with case series from Southeast Asia and Northern Australia for the most part, in terms of risk factors associated with infection and factors influencing mortality. Differences included clinical presentation of pneumonia which was notably lower than that reported in Southeast Asia and Northern Australia; a higher proportion of neurological and parotid abscess presentation; and a lower CFR compared to that reported in case series in Southeast Asia. Ab

关键词： Melioidosis India Bangladesh burkholderia pseudomallei Environmental

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A Case on AcutePericarditis

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中华医学杂志(英文版) 2016年第18期129卷 2256-2257页

作者： Xing-JunCai Yi-JiangHuang Yi-HuiFu Department of Respiratory Hainan General Hospital Haikou Hainan 570311 China

关键词： burkholderia pseudomallei Melioidosis Pericarditis Tuberculosis

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