McElheny Christi L, Iovleva Alina, Chen Nathalie, Woods Dominic, Pradhan Akansha, Sonnabend Jonah L, Matunis Aidan R, Raabe Nathan J, Lee Janet S, Trevejo-Nuñez Giraldina, Van Tyne Daria, Doi Yohei
Center for Innovative Antimicrobial Therapy, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Infect Immun. 2025 Jan 31;93(1):e0048624. doi: 10.1128/iai.00486-24. Epub 2024 Dec 11.
Hypervirulent (hvKp) strains are considered to be relatively rare in the United States, but cases are increasingly reported. We prospectively and serially collected clinical isolates identified in respiratory specimens at a health system in Western Pennsylvania between 2020 and 2022. A total of 273 . isolates from 216 unique patients were analyzed for markers of hypervirulence by both string test for a hypermucoid phenotype and multiplex PCR to detect isolates carrying cardinal virulence genes , , , and . Of the 273 isolates, 13 (4.8%) tested positive by string test including 11 nonduplicate isolates, and two of these (0.7%) were positive by PCR for virulence genes , , , and . The latter two putative hvKp strains, belonging to sequence types ST23-K1 and ST86-SLV-K2, possessed pLVPK-like plasmids, and were collected from community-associated infections in individuals without known travel histories. Both putative hvKp strains and two additional string test-positive strains were resistant to killing by human serum. The hvKp strains caused significant pneumonia in mice infected by oropharyngeal aspiration, with significantly higher weight loss and increased bacterial burden in the lungs of mice infected with the KL1 (ST23) strain compared to the KL2 (ST86-SLV) strain. We also observed decreased survival of mice infected with the KL1 strain compared to the KL2 strain. These findings add to the growing body of evidence suggesting that hvKp strains, once considered endemic to Asia, may now be circulating in North America.IMPORTANCECertain lineages of are increasingly recognized to cause severe community-associated infection, but information on their prevalence in the United States is limited. In a prospective, sequential cohort of 273 . respiratory isolates, we identified two of them as genetically defined hypervirulent . The isolates were from local residents who developed community-onset pneumonia, suggesting that hypervirulent may already be present in the community.
高毒力肺炎克雷伯菌（hvKp）菌株在美国被认为相对罕见，但报告的病例越来越多。我们在2020年至2022年期间，前瞻性地、连续收集了宾夕法尼亚西部一个卫生系统呼吸道标本中鉴定出的临床分离株。对来自216名独特患者的总共273株分离株进行了分析，通过检测高黏液样表型的拉丝试验和多重聚合酶链反应（PCR）来检测携带主要毒力基因、、、和的分离株。在这273株分离株中，13株（4.8%）拉丝试验呈阳性，包括11株非重复分离株，其中两株（0.7%）毒力基因、、、和的PCR检测呈阳性。后两株推定的hvKp菌株，属于序列类型ST23-K1和ST86-SLV-K2，拥有类似pLVPK的质粒，并且是从无已知旅行史的个体的社区获得性感染中分离得到的。这两株推定的hvKp菌株以及另外两株拉丝试验阳性菌株对人血清杀伤具有抗性。hvKp菌株通过口咽吸入感染小鼠时会引起严重肺炎，与感染KL2（ST86-SLV）菌株的小鼠相比，感染KL1（ST23）菌株的小鼠体重减轻更显著，肺部细菌载量增加。我们还观察到，与感染KL2菌株的小鼠相比，感染KL1菌株的小鼠存活率降低。这些发现进一步证明，曾经被认为是亚洲特有的hvKp菌株现在可能正在北美传播。重要性某些肺炎克雷伯菌谱系越来越被认为会引起严重的社区获得性感染，但它们在美国的流行情况信息有限。在一个前瞻性的、连续的队列中，对273株呼吸道分离株进行研究，我们鉴定出其中两株为基因定义的高毒力肺炎克雷伯菌。这些分离株来自发生社区获得性肺炎的当地居民，这表明高毒力肺炎克雷伯菌可能已经在社区中存在。
