Clinical and genomic analysis of virulence-related genes in bloodstream infections caused by Acinetobacter baumannii

ABSTRACT

Acinetobacter baumannii has emerged as a common cause of bloodstream infections, which is associated with high mortality and long periods of hospitalization. To advance the medical care of our patients, the study was designed to identify microbial characteristics associated with poor clinical outcomes. A collection of 32 A. baumannii bloodstream isolates with diverse genetic backgrounds (as determined by multilocus sequence typing) was studied. These isolates were recovered by unique patients (18 males, 14 females; age range: 17 days to 87 years) between 2011 and 2018. A sequential screening approach (cross-referencing analyses using different endpoints) was used to identify isolates with the best correlation between bacterial virulence and clinical prognosis. Isolates associated with more rapid in vitro growth rate, shorter median survival time in pre-clinical infection models, and hospital mortality were selected as candidates for high virulence, while those with opposite characteristics were selected as controls with low virulence. Whole genome sequencing was undertaken in the most promising clinical isolates. We found five virulence genes (beta-hemolysin/cytolysin, Cpi-1a + Cpi-1 (SPI-1 like), enhanced entry proteins, FbpABC, Paa) and 1 secretory system (T6SS) only present in a highly virulent isolate (AB23), compared to a low virulence control isolate (AB6). These genetic elements could be associated with the poor prognosis of A. baumannii bacteraemia and further investigations are warranted.

KEYWORDS:

• Gram-negative bacteria
• bacteraemia
• whole genome sequencing
• outcome

Acknowledgments

The authors would like to thank Novogene Co., Ltd. (Beijing, China) for their whole genome sequencing and comparative analysis.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are openly available in National Center for Biotechnology Information (NCBI) at https://www.ncbi.nlm.nih.gov/, accession numbers: JAOAOM000000000, JAOAON000000000, JAOANQ000000000, JAOAOO000000000, and JAOBQI000000000, respectively.

Ethics statements

All procedures involving human participants were performed in accordance with the ethical standards of Shenzhen University (Shenzhen, China) and the 1964 Helsinki declaration and its later amendments, or comparable ethical standards. In view of the retrospective nature of the study, formal consent is not required. All vertebrate animals were cared for in accordance with the highest humane and ethical standards, as approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Houston (Houston, USA).

Additional information

Funding

The study was supported in part by the Sanming Project of Medicine (Shenzhen, China) and the National Institutes of Health (5R01AI140287-04).