Lyb-2-4, a unique genomic region of hypervirulent carbapenem-resistant Acinetobacter baumannii

Abstract

Acinetobacter baumannii is an important human pathogen due to its multi-drug 25 resistance, but is usually with low-grade virulence. Although a mouse model revealed different 26 virulence grades of clinical carbapenem-resistant A. baumannii (CRAB) strains, the genetic basis 27 remains unknown. We collected 61 CRAB isolates from intensive care unit of Shenzhen People's 28Hospital (Shenzhen, China), and analyzed them used whole genome sequencing (WGS), 29 multilocus sequence typing (MLST) and core genome MLST (cgMLST), transmission chain 30 reconstruction and Comparative genomic tools. A mouse pneumonia model was used to confirm 31 the hypervirulent phenotype. Eleven complex types (CT) were identified based on core genome 32 multilocus sequence typing scheme. CT512 showed higher transmissibility and bloodstream 33 infection rates than other CTs. A genomic region Lyb-2-4 was shared by CT512 and CT2092 but 34 not CT2085. The mortality rates of patient infected with CRAB harboring Lyb-2-4 was 35 significantly higher than those infected with CRAB isolates without Lyb-2-4 (77.8% vs 24.5%, p < 36 0.01). In the mouse model, the survival rates of strains containing the Lyb-2-4 region (LAC-4, 37 5122 and 2092) were significantly lower than for strains without Lyb-2-4 (7152, 71517, 20859 and 38 ATCC17978). One open reading frame (ORF) was a marker for the presence of Lyb-2-4, and PCR 39 of a segment of this ORF, designated as hvcT, served as a tag for hypervirulent CRAB. Our study 40 should be very useful in advising the clinician to implement medical intervention earlier, and also 41 making the worldwide surveillance of these hypervirulent CRAB strains easier. 42 IMPORTANCE Hypervirulent CRAB strains are expected to pose a threat to human health 43 because infection of these strains is associated with high mortality and multidrug resistance. The 44 rapid hypervirulent CRAB identification assay will facilitate prompt medical intervention. Our 45 findings should provoke surveillance for hypervirulent CRAB strains harboring Lyb-2-4 in other 46 countries. Further research should focus on the mechanism of hypervirulence, the acquisition of 47 1 Dijkshoorn L, Nemec A, Seifert H. An increasing threat in hospitals: multidrug-resistant Acinetobacter 302 baumannii. Nature Rev Microbiol 2007; 5: 939-51. 303 2 Evans BA, Hamouda A, Amyes SG. The rise of carbapenem-resistant Acinetobacter baumannii. Curr Pharm