Long-read sequencing reveals genetic adaptation of Bartonella adhesin a among different Bartonella henselae isolates

  • Bartonella henselae is the causative agent of cat scratch disease and other clinical entities such as endocarditis and bacillary angiomatosis. The life cycle of this pathogen, with alternating host conditions, drives evolutionary and host-specific adaptations. Human, feline, and laboratory adapted B. henselae isolates often display genomic and phenotypic differences that are related to the expression of outer membrane proteins, for example the Bartonella adhesin A (BadA). This modularly-structured trimeric autotransporter adhesin is a major virulence factor of B. henselae and is crucial for the initial binding to the host via the extracellular matrix proteins fibronectin and collagen. By using next-generation long-read sequencing we demonstrate a conserved genome among eight B. henselae isolates and identify a variable genomic badA island with a diversified and highly repetitive badA gene flanked by badA pseudogenes. Two of the eight tested B. henselae strains lack BadA expression because of frameshift mutations. We suggest that active recombination mechanisms, possibly via phase variation (i.e., slipped-strand mispairing and site-specific recombination) within the repetitive badA island facilitate reshuffling of homologous domain arrays. The resulting variations among the different BadA proteins might contribute to host immune evasion and enhance long-term and efficient colonisation in the differing host environments. Considering the role of BadA as a key virulence factor, it remains important to check consistently and regularly for BadA surface expression during experimental infection procedures.

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Author:Arno ThibauGND, Katharina HippORCiDGND, Diana Jaqueline Vaca LlerenaORCiDGND, Sounak Chowdhury, Johan MalmströmORCiD, Athanasios SaragliadisORCiD, Wibke Ballhorn, Dirk LinkeORCiD, Volkhard A. J. KempfORCiDGND
Parent Title (English):Frontiers in microbiology
Publisher:Frontiers Media
Place of publication:Lausanne
Document Type:Article
Date of Publication (online):2022/02/07
Date of first Publication:2022/02/07
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/06/21
Tag:Bartonella adhesin A; PacBio SMRT sequencing; genetic variability; host matrix- pathogen interaction; trimeric autotransporters adhesin
Issue:art. 838267
Article Number:838267
Page Number:17
First Page:1
Last Page:17
This research was supported by the Viral and Bacterial Adhesin Network Training (ViBrANT) Programme funded by the European Union’s HORIZON 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement No 765042 (to VK, JM, and DL), by the Robert Koch-Institute, Berlin, Germany (Bartonella consiliary laboratory, 1369-354, to VK), and by the Deutsche Forschungsgemeinschaft (DFG FOR 2251 “Adaptation and persistence of Acinetobacter baumannii” to VK).
The raw data supporting the conclusions of this article will be made available by the authors upon request, without undue reservation. The genome sequences of all sequenced B. henselae isolates, together with their corresponding SRA data, have been deposited in the NCBI GenBank database under BioProject PRJNA720375 with the following genome accession numbers: CP072904 (Marseille), CP072903 (ATCC49882T var-1), CP072902 (ATCC49882T var-2), CP072901 (Berlin-I), CP072900 (G-5436), CP072899 (88-64 Oklahoma), CP072898 (FR96/BK38), and CP072897 (FR96/BK3) (Supplementary Table 1). The genomic sequence of badA from B. henselae Marseille was deposited separately under the GenBank accession number MK993576.1.
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International