Giám sát di truyền về tính năng siêu độc và đa kháng thuốc trong Klebsiella pneumoniae xâm lấn từ Nam và Đông Nam Á

Springer Science and Business Media LLC - Tập 12 Số 1 - 2020
Kelly L. Wyres1, To Nguyen Thi Nguyen2, Margaret Lam1, Louise M. Judd1, Nguyễn Văn Vĩnh Châu3, David A. B. Dance4, Margaret Ip5, Abhilasha Karkey6, Clare Ling6, Thyl Miliya7, Paul N. Newton4, Nguyen Phu Huong Lan3, Amphone Sengduangphachanh4, Paul Turner6, Balaji Veeraraghavan8, Phat Voong Vinh2, Manivanh Vongsouvath4, Nicholas R. Thomson9, Stephen Baker10, Kathryn E. Holt9
1Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Victoria, 3004, Australia
2Hospital of Tropical Diseases, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
3the Hospital of Tropical Diseases, Ho Chi Minh City, Vietnam
4Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People’s Democratic Republic
5Department of Microbiology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
6Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK
7Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia
8Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India
9London School of Hygiene and Tropical Medicine, London, UK
10Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID) Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK

Tóm tắt

Tóm tắt Thông tin nền Klebsiella pneumoniae là nguyên nhân hàng đầu gây nhiễm trùng huyết (BSI). Các chủng sản sinh beta-lactamase phổ rộng (ESBLs) hoặc carbapenemase được coi là mầm bệnh ưu tiên toàn cầu, mà cần phải có những chiến lược điều trị và phòng ngừa mới một cách khẩn thiết, do các lựa chọn điều trị nghiêm trọng bị hạn chế. Nam và Đông Nam Á là những trung tâm chính cho K. pneumoniae kháng kháng sinh (AMR) và cũng cho những chủng “siêu độc” có tính nhạy cảm với kháng sinh, được lấy từ cộng đồng. Sự xuất hiện của các chủng AMR siêu độc và thiếu dữ liệu về sự đa dạng của exopolysaccharide đặt ra thách thức cho các chiến lược kiểm soát BSI do K. pneumoniae gây ra trên toàn cầu. Phương pháp Chúng tôi đã tiến hành một nghiên cứu dịch tễ học di truyền hồi cứu trên 365 mẫu BSI K. pneumoniae từ bảy cơ sở chăm sóc sức khỏe lớn ở Nam và Đông Nam Á, trích xuất thông tin lâm sàng liên quan (AMR, độ độc, loci kháng nguyên K và O) bằng cách sử dụng Kleborate, một công cụ phân loại di truyền đặc thù cho K. pneumoniae. Kết quả Các mẫu BSI K. pneumoniae rất đa dạng, bao gồm 120 loại chuỗi đa vị trí (STs) và 63 loci K. Tần suất gen ESBL và carbapenemase lần lượt là 47% và 17%. Locus tổng hợp aerobactin (iuc), liên quan đến siêu độc, được phát hiện trong 28% các mẫu. Quan trọng, 7% các mẫu có gen iuc cùng với gen ESBL và/hoặc carbapenemase. Điều này đại diện cho sự hội tụ về kiểu gen AMR-độc tính, mà thường được coi là một hiện tượng hiếm nhưng lại đặc biệt phổ biến trong BSI ở Nam Á (17%). Khả năng đáng lo ngại nhất, chúng tôi đã xác định bảy plasmid mới mang cả gen iuc và gen AMR, làm dấy lên khả năng chuyển giao đồng thời các kiểu hình này giữa các K. pneumoniae. Kết luận K. pneumoniae BSI ở Nam và Đông Nam Á do các ST khác với những ST chiếm ưu thế ở các khu vực khác gây ra, và với tần suất cao hơn của các yếu tố độc tính thu nhận. K. pneumoniae mang cả gen iuc và gen AMR cũng được phát hiện với tỷ lệ cao hơn so với các báo cáo ở nơi khác. Nghiên cứu chứng minh rằng giám sát dựa trên genomics—báo cáo đầy đủ hồ sơ phân tử bao gồm STs, AMR, độ độc và thông tin loci huyết thanh—có thể giúp tiêu chuẩn hóa các so sánh giữa các địa điểm và xác định sự khác biệt khu vực trong quần thể mầm bệnh.

Từ khóa


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