Afzal Madeeha, Vijay Ajay Kumar, Stapleton Fiona, Willcox Mark D P
School of Optometry and Vision Science, University of New South Wales, Sydney, NSW 2052, Australia.
Antibiotics (Basel). 2022 Jul 27;11(8):1011. doi: 10.3390/antibiotics11081011.
Staphylococcus aureus is a major cause of ocular infectious (corneal infection or microbial keratitis (MK) and conjunctivitis) and non-infectious corneal infiltrative events (niCIE). Despite the significant morbidity associated with these conditions, there is very little data about specific virulence factors associated with the pathogenicity of ocular isolates. A set of 25 S. aureus infectious and niCIEs strains isolated from USA and Australia were selected for whole genome sequencing. Sequence types and clonal complexes of S. aureus strains were identified by using multi-locus sequence type (MLST). The presence or absence of 128 virulence genes was determined by using the virulence finder database (VFDB). Differences between infectious (MK + conjunctivitis) and niCIE isolates from USA and Australia for possession of virulence genes were assessed using the chi-square test. The most common sequence types found among ocular isolates were ST5, ST8 while the clonal complexes were CC30 and CC1. Virulence genes involved in adhesion (ebh, clfA, clfB, cna, sdrD, sdrE), immune evasion (chp, esaD, esaE, esxB, esxC, esxD), and serine protease enzymes (splA, splD, splE, splF) were more commonly observed in infectious strains (MK + conjunctivitis) than niCIE strains (p = 0.004). Toxin genes were present in half of infectious (49%, 25/51) and niCIE (51%, 26/51) strains. USA infectious isolates were significantly more likely to possess splC, yent1, set9, set11, set36, set38, set40, lukF-PV, and lukS-PV (p < 0.05) than Australian infectious isolates. MK USA strains were more likely to possesses yent1, set9, set11 than USA conjunctivitis strains (p = 0.04). Conversely USA conjunctivitis strains were more likely to possess set36 set38, set40, lukF-PV, lukS-PV (p = 0.03) than MK USA strains. The ocular strain set was then compared to 10 fully sequenced non-ocular S. aureus strains to identify differences between ocular and non-ocular isolates. Ocular isolates were significantly more likely to possess cna (p = 0.03), icaR (p = 0.01), sea (p = 0.001), set16 (p = 0.01), and set19 (p = 0.03). In contrast non-ocular isolates were more likely to possess icaD (p = 0.007), lukF-PV, lukS-PV (p = 0.01), selq (p = 0.01), set30 (p = 0.01), set32 (p = 0.02), and set36 (p = 0.02). The clones ST5, ST8, CC30, and CC1 among ocular isolates generally reflect circulating non-ocular pathogenic S. aureus strains. The higher rates of genes in infectious and ocular isolates suggest a potential role of these virulence factors in ocular diseases.
金黄色葡萄球菌是眼部感染（角膜感染或微生物性角膜炎（MK）和结膜炎）以及非感染性角膜浸润性病变（niCIE）的主要病因。尽管这些病症会导致严重的发病率，但关于眼部分离株致病性相关的特定毒力因子的数据却非常少。从美国和澳大利亚分离出的一组25株金黄色葡萄球菌感染性和niCIE菌株被选来进行全基因组测序。通过多位点序列分型（MLST）来鉴定金黄色葡萄球菌菌株的序列类型和克隆复合体。利用毒力因子查找数据库（VFDB）来确定128个毒力基因的有无。使用卡方检验评估美国和澳大利亚的感染性（MK + 结膜炎）与niCIE分离株在毒力基因拥有情况上的差异。眼部分离株中最常见的序列类型是ST5、ST8，而克隆复合体是CC30和CC1。与黏附（ebh、clfA、clfB、cna、sdrD、sdrE）、免疫逃避（chp、esaD、esaE、esxB、esxC、esxD）以及丝氨酸蛋白酶（splA、splD、splE、splF）相关的毒力基因在感染性菌株（MK + 结膜炎）中比在niCIE菌株中更常见（p = 0.004）。毒素基因在一半的感染性（49%，25/51）和niCIE（51%，26/51）菌株中存在。美国的感染性分离株比澳大利亚的感染性分离株更有可能拥有splC、yent1、set9、set11、set36、set38、set40、lukF - PV和lukS - PV（p < 0.05）。美国的MK菌株比美国的结膜炎菌株更有可能拥有yent1、set9、set11（p = 0.04）。相反，美国的结膜炎菌株比美国的MK菌株更有可能拥有set36、set38、set40、lukF - PV、lukS - PV（p = 0.03）。然后将眼部菌株组与10株全基因组测序的非眼部金黄色葡萄球菌菌株进行比较，以确定眼部和非眼部分离株之间的差异。眼部分离株更有可能拥有cna（p = 0.03）、icaR（p = 0.01）、sea（p = 0.001）、set16（p = 0.01）和set19（p = 0.03）。相比之下，非眼部分离株更有可能拥有icaD（p = 0.007）、lukF - PV、lukS - PV（p = 0.01）、selq（p = 0.01）、set30（p = 0.01）、set32（p = 0.02）和set36（p = 0.02）。眼部分离株中的ST5、ST8、CC30和CC1克隆通常反映了循环中的非眼部致病性金黄色葡萄球菌菌株。感染性和眼部分离株中较高的基因频率表明这些毒力因子在眼部疾病中可能发挥作用。
