Biology of the relationship of Integrative and Conjugative Elements (ICEs) of the SXT/R391 family with its natural host Proteus mirabilis

• Grant number: 22/03986-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2022
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Rodrigo da Silva Galhardo
• Grantee: Douglas Lyra de Holanda Fonseca
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The association of Mobile Genetic Elements (MGEs) with the increase in the number of multidrug-resistant bacteria has become increasingly evident, however the biology of the relationship of these elements with their hosts is a complex aspect. Integrative and Conjugative Elements (ICEs) of the SXT/R391 family are MGEs that integrate into the chromosome and disseminate resistance genes mainly between Vibrio, Providencia and Proteus. However, in addition to resistance genes and their regulation, these elements may harbor genes with varied functions, which may confer adaptive advantages to their hosts, such as the increase in mutagenic capacity due to the presence of homologs of polymerase V encoded by the rumAB operon. Recently, our group identified Brazilian clinical strains of P. mirabilis containing SXT/R391 ICEs, one of which is the globally distributed ICEPmiJpn1 with a resistance marker for ampicillin. We carried out the construction of 5 pairs of isogenic strains containing or not this ICE, which allowed us to evaluate the influence of this element in aspects of the physiology of P. mirabilis, verifying that the ICE did not impact the recognition capacity or the fitness of this bacterium, it increased biofilm formation of one strain and slightly decreased swarming of P. mirabilis. We also evaluated that the presence of rumAB is important for ICE conjugation during genotoxic damage and that variations in the frequency of spontaneous conjugation occur between strains. Studies on ICEs have evaluated that these elements are able to use host mechanisms, such as the SOS response, to induce greater transfer and ensure its perpetuation. Our study seeks to evaluate aspects of the relationship between ICEs of the SXT/R391 family and its natural host P. mirabilis, evaluating the influence of this element on aspects of the physiology and pathogenesis of P. mirabilis through infection in Galleria mellonella and persistent cell assays, in addition to investigating aspects of the host that may influence the conjugative capacity of the ICE under study. Finally, we want to evaluate impacts caused by the ICE on the transcriptional profile of P. mirabilis without and after DNA damage, verifying which changes occur after ICE insertion and how this influences the host during the SOS response. (AU)