Sex is stress. In the depicted model, expression and assembly of the conjugative T4S complex activate extracytoplasmic and cytoplasmic stress regulons. The assembly of a functional T4S complex leads to extracytoplasmic stress that is sensed by the CpxAR system. The phosphorylated CpxR response regulator (CpxR-P) stimulates the transcription of periplasmic folding factors and proteases. These proteins may play a protective role or may be needed for efficient assembly of the T4S machinery or for degradation of excessive Tra proteins. A cytoplasmic stress response which induces the transcription of classical heat shock genes is mediated via increased steady-state levels of the alternative sigma factor σ32 (encoded by the rpoH gene). We assume that chaperons such as DnaJK-GrpE and/or GroEL/S bind to Tra proteins in the cytoplasm, thereby increasing the half-life of σ32. The induced proteins might be involved in degradation of regulatory Tra proteins and in conferring export competence to precursors of T4S proteins. Our data suggest that the two stress networks are connected via CpxR-P-dependent transcriptional activation of rpoH. OM, outer membrane; IM, inner membrane; PG, peptidoglycan.