Evolutionary Dynamics of Pathoadaptation Revealed by Three Independent Acquisitions of the VirB/D4 Type IV Secretion System in Bartonella.
The α-proteobacterial genus Bartonella comprises a group of ubiquitous mammalian pathogens that are studied as a model for the evolution of bacterial pathogenesis. Vast abundance of two particular phylogenetic lineages of Bartonella had been linked to enhanced host adaptability enabled by lineage-specific acquisition of a VirB/D4 type IV secretion system (T4SS) and parallel evolution of complex effector repertoires. However, the limited availability of genome sequences from one of those lineages as well as other, remote branches of Bartonella has so far hampered comprehensive understanding of how the VirB/D4 T4SS and its effectors called Beps have shaped Bartonella evolution. Here, we report the discovery of a third repertoire of Beps associated with the VirB/D4 T4SS of B. ancashensis, a novel human pathogen that lacks any signs of host adaptability and is only distantly related to the two species-rich lineages encoding a VirB/D4 T4SS. Furthermore, sequencing of ten new Bartonella isolates from under-sampled lineages enabled combined in silico analyses and wet lab experiments that suggest several parallel layers of functional diversification during evolution of the three Bep repertoires from a single ancestral effector. Our analyses show that the Beps of B. ancashensis share many features with the two other repertoires, but may represent a more ancestral state that has not yet unleashed the adaptive potential of such an effector set. We anticipate that the effectors of B. ancashensis will enable future studies to dissect the evolutionary history of Bartonella effectors and help unraveling the evolutionary forces underlying bacterial host adaptation.
Focal Area Infection Biology, Biozentrum, University of Basel, Switzerland.
Alexander
A
Harms
Department of Fundamental Microbiology, University of Lausanne, Switzerland.
Francisca H I D
FH
Segers
Focal Area Infection Biology, Biozentrum, University of Basel, Switzerland.
Maxime
M
Quebatte
Focal Area Infection Biology, Biozentrum, University of Basel, Switzerland.
Claudia
C
Mistl
Focal Area Infection Biology, Biozentrum, University of Basel, Switzerland.
Pablo
P
Manfredi
Focal Area Infection Biology, Biozentrum, University of Basel, Switzerland.
Jonas
J
Körner
Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis.
Bruno B
BB
Chomel
Bacterial Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, Colorado.
Michael
M
Kosoy
Laboratory of Veterinary Public Health, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Tokyo, Japan.
Soichi
S
Maruyama
Department of Fundamental Microbiology, University of Lausanne, Switzerland.
Philipp
P
Engel
Focal Area Infection Biology, Biozentrum, University of Basel, Switzerland.
Christoph
C
Dehio
D001426:Bacterial Proteins / Q000235:genetics; D058947:Bacterial Secretion Systems / Q000235:genetics*; D001473:Bartonella / Q000235:genetics* / Q000472:pathogenicity; D001474:Bartonella Infections / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D019143:Evolution, Molecular; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D010802:Phylogeny; D000069319:Type IV Secretion Systems / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics
D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D000069319:Type IV Secretion Systems; D037521:Virulence Factors
AMPylation; bacterial effector; filamentation induced by cAMP; parallel evolution