The type IV secretion system of Patescibacteria is homologous to the bacterial monoderm conjugation machinery

Abstract

The Candidate Phyla Radiation, also known as Patescibacteria, represents a vast and diverse division of bacteria that has come to light via culture-independent omics technologies. Their limited biosynthetic capacity, along with evidence of their growth as obligate epibionts on other bacteria, suggests a broad reliance on host organisms for their survival. Nevertheless, our under-standing of the molecular mechanisms governing their metabolism and lifestyle remains limited. The type IV secretion system (T4SS) represents a superfamily of translocation systems with a wide range of functional roles. T4SS genes have been identi-fied in the Patescibacteria class Saccharimonadia as essential for their epibiotic growth. In this study, we used a comprehensive bioinformatics approach to investigate the diversity and distribution of T4SS within Patescibacteria. The phylogenetic analysis of the T4SS signature protein VirB4 suggests that most of these proteins cluster into a distinct monophyletic group with a shared ancestry to the MPFFATA class of T4SS. This class is found in the conjugative elements of Firmicutes, Actinobacteria, Tenericutes and Archaea, indicating a possible horizontal gene transfer from these monoderm micro-organisms to Patescibacteria. We iden-tified additional T4SS components near virB4, particularly those associated with the MPFFATA class, as well as homologues of other T4SS classes, such as VirB2-like pilins, and observed their varied arrangements across different Patescibacteria classes. The absence of a relaxase in most of these T4SS clusters suggests that the system has been co-opted for other functions in Patescibacteria. The proximity of T4SS components to the origin of replication (gene dnaA) in some Patescibacteria suggests a potential mechanism for increased expression. The broad ubiquity of a phylogenetically distinct T4SS, combined with its chromosomal location, underscores the significance of T4SS in the biology of Patescibacteria.This work was supported by the Spanish Ministry of Science and Innovation (Grant MCIN/AEI/10.13039/501100011033 PID2020-117923GB-I00 to M.P.G.-B.), the Spanish Ministry of Economy, Industry and Competitiveness (FLEX3GEN PID2020-118052GB-I00, cofounded with FEDER funds to F.R-V) and the Spanish Ministry of Universities (predoctoral contract FPU20/04579 to M.d.M.Q.-C.). P.J.C.-Y. work was funded by a Post-Doctoral Fellowship from the Fundación Alfonso Martín Escudero, Spain, and is currently supported by a Marie Sklodowska-Curie postdoctoral fellowship granted by the Horizon Europe programme (1011052332-CYANORUB) and funded by the UKRI (grant ref: EP/Y028384/1)