Lewis Joseph M, Mphasa Madalitso, Banda Rachel, Beale Mathew A, Mallewa Jane, Heinz Eva, Thomson Nicholas R, Feasey Nicholas A
Malawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi.
Liverpool School of Tropical Medicine, Liverpool, UK.
Microb Genom. 2022 Mar;8(3). doi: 10.1099/mgen.0.000778.
Members of the species complex, particularly subsp. are antimicrobial resistance (AMR) associated pathogens of global importance, and polyvalent vaccines targeting O-antigens are in development. Whole-genome sequencing has provided insight into O-antigen distribution in the species complex as well as population structure and virulence determinants, but genomes from sub-Saharan Africa are underrepresented in global sequencing efforts. We therefore carried out a genomic analysis of extended-spectrum beta-lactamase (ESBL)-producing species complex isolates colonizing adults in Blantyre, Malawi. We placed these isolates in a global genomic context, and compared colonizing to invasive isolates from the main public hospital in Blantyre. In total, 203 isolates from stool and rectal swabs from adults were whole-genome sequenced and compared to a publicly available multicounty collection and previously sequenced Malawian and Kenyan isolates from blood or sterile sites. We inferred phylogenetic relationships and analysed the diversity of genetic loci linked to AMR, virulence, capsule and LPS O-antigen (O-types). We find that the diversity of Malawian subsp. isolates represents the species' population structure, but shows distinct local signatures concerning clonal expansions. Siderophore and hypermucoidy genes were more frequent in invasive versus colonizing isolates (present in 13 % vs 1 %) but still generally lacking in most invasive isolates. O-antigen population structure and distribution was similar in invasive and colonizing isolates, with O4 more common (14%) than in previously published studies (2-5 %). We conclude that host factors, pathogen opportunity or alternate virulence loci not linked to invasive disease elsewhere are likely to be the major determinants of invasive disease in Malawi. Distinct ST and O-type distributions in Malawi highlight the need to sample locations where the burden of invasive disease is greatest to robustly define secular trends in diversity to assist in the development of a useful vaccine. Colonizing and invasive isolates in Blantyre are similar, hence O-typing of colonizing isolates may be a rapid and cost-effective approach to describe global diversity and guide vaccine development.
该菌种复合体的成员，尤其是亚种，是具有全球重要性的抗菌药物耐药性（AMR）相关病原体，针对O抗原的多价疫苗正在研发中。全基因组测序为了解该菌种复合体中O抗原的分布以及种群结构和毒力决定因素提供了线索，但撒哈拉以南非洲地区的基因组在全球测序工作中代表性不足。因此，我们对马拉维布兰太尔成年人体内产超广谱β-内酰胺酶（ESBL）的该菌种复合体分离株进行了基因组分析。我们将这些分离株置于全球基因组背景下，并将其与布兰太尔主要公立医院的侵袭性分离株进行比较。总共对来自成人粪便和直肠拭子的203株分离株进行了全基因组测序，并与公开可用的多县样本以及先前测序的来自血液或无菌部位的马拉维和肯尼亚分离株进行比较。我们推断了系统发育关系，并分析了与AMR、毒力、荚膜和LPS O抗原（O型）相关的基因座的多样性。我们发现马拉维亚种分离株的多样性代表了该物种的种群结构，但在克隆扩增方面显示出明显的本地特征。与定殖分离株相比，铁载体和高黏液形成基因在侵袭性分离株中更常见（分别为13%和1%），但在大多数侵袭性分离株中仍然普遍缺乏。侵袭性和定殖分离株中的O抗原种群结构和分布相似，O4比以前发表的研究中更常见（14%，之前为2%-5%）。我们得出结论，宿主因素、病原体机会或与其他地方侵袭性疾病无关的替代毒力基因座可能是马拉维侵袭性疾病的主要决定因素。马拉维独特的ST和O型分布凸显了在侵袭性疾病负担最大的地点进行采样的必要性，以有力地确定该菌种多样性的长期趋势，从而有助于开发有效的疫苗。布兰太尔的定殖和侵袭性分离株相似，因此对定殖分离株进行O分型可能是一种快速且经济高效的方法，用于描述全球多样性并指导疫苗开发。
