# Mitigation of Stress Responses By Protein Transfer Through Conjugation Machines

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $234,000

## Abstract

PROJECT SUMMARY
Conjugation systems are widely known for their roles in disseminating mobile genetic elements (MGEs) and
cargoes of antibiotic resistance, fitness, and virulence genes among many species of bacteria. The enormous
medical problem associated with MGE-transmitted antibiotic resistance is enhanced by the fact that
conjugation systems also code for surface adhesins or conjugative pili that promote intercellular contacts
favoring transmission and establishment of robust, antibiotic-resistant biofilm communities. Furthermore,
various environmental stresses, including antibiotics, have been shown to stimulate MGE transmission
whereas, conversely, MGE transfer induces the SOS response and activates movement of integrons, which
are reservoirs of antibiotic resistance genes. Adding to the myriad of ways conjugation can impact
development of antibiotic resistance and genome evolution, we have shown that a consequence of
conjugation-induced SOS is the elevated accumulation of mutations in recipient cells. To mitigate the
deleterious consequences of mating-induced mutation, here termed MIM, many conjugative elements carry
genes such as psiB and ssb whose products suppress the SOS response. In our studies of a model F plasmid,
pED208, we discovered that PsiB and SSB are delivered through the conjugation channel, also known as a
type IV secretion system (T4SS), to recipient cells. Furthermore, translocated PsiB and SSB suppress both the
SOS response and MIM in transconjugants. ssb and psiB genes are carried by the maintenance/leading
regions (MLRs) of F plasmids and many other conjugative plasmids, as are several other genes whose
products are predicted to promote establishment of the MGE following transfer to recipient cells By use of a
robust and quantitative Cre Recombinase Assay for Translocation (CRAfT), we have shown that pED208
conjugatively transfers at least 9 MLR-encoded proteins, as well as 7 chromosomally-encoded proteins with
predicted or known functions in DNA metabolism and stress mitigation. In Aim 1, we will define the functional
interplay of PsiB, SSB, and a third protein, PsiA, in modulating the SOS response and MIM in donor and
recipient cells during conjugation. We will also evaluate the broader biological roles of PsiB and SSB
translocation through studies of other model conjugation systems and intra- and interspecies matings, and by
assessing effects of exogenous stresses on MGE transfer and PsiB/SSB mitigation of stress responses and
mutation. In Aim 2, we will identify and characterize the biological functions of other translocated MLR proteins
encoded by the model F plasmid, pED208. We will define the repertoire of chromosomally-encoded
translocated proteins, and initiate studies exploring biological functions focusing initially on testing a hypothesis
that mating induces the oxidative stress response and translocated SodA mitigates this stress response.
Results of these studies will significantly expand our understandin...

## Key facts

- **NIH application ID:** 10195321
- **Project number:** 1R21AI159970-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** PETER j. CHRISTIE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $234,000
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10195321

## Citation

> US National Institutes of Health, RePORTER application 10195321, Mitigation of Stress Responses By Protein Transfer Through Conjugation Machines (1R21AI159970-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10195321. Licensed CC0.

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