Furthermore, L. pneumophila in stationary phase also displays shortened cell body, flagellin expression, pigment accumulation and reduced sodium sensitivity. These attributes, together with virulence markers such as cytotoxicity, intracellular growth and phagocytosis, are recognized as the transmission traits of L. pneumophila [11, 13]. On the other hand, the in vitro-cultured stationary-phase L. pneumophila can achieve further differentiation to the cyst-like, Dibutyryl-cAMP molecular weight hyper-infectious and resilient mature intracellular

form (MIF) in aquatic environment or in specific mammalian cell lines. MIF is considered as an “”in vivo stationary-phase form”" while owning different outer membrane structure and protein composition compared with the stationary-phase form [14, 15]. In addition, an in vivo transcriptome of L. pneumophila was performed and exhibited the genes strongly induced in intracellular replicative or transmissive phase, respectively, which also LY2874455 datasheet revealed several virulence or transmission related genes specially induced intracellularly, confirming the dissimilarity between the in vitro- and in vivo- transmissive/stationary phase [16]. A complicated gene network has been implicated in

the regulation of transmission traits in L. pneumophila. For example, the sigma factor RpoS, the two-component system LetA/LetS, and the quorum sensing regulator LqsR have all been shown to facilitate the expression of transmission traits [10, 11, 13, 17, 18]. CsrA, a global repressor of transmission [19],

also appears to be tightly regulated by several factors NVP-BGJ398 in vivo such as PmrA (positive regulator of several Dot/Icm-translocated effector proteins) and rsmYZ (two non-coding RNAs) [20, 21]. In addition, CpxR has been found to activate transcription of several genes encoding components of the Dot/Icm complex Epothilone B (EPO906, Patupilone) as well as several Dot/Icm-translocated effectors [22, 23]. The concerted action of these regulators not only contributes to the display of transmission traits, but also plays a vital role in the re-entry into the replicative phase [11, 13, 19, 20, 24]. Proteolysis of detrimental and misfolded proteins is critically important for protein quality control and cellular homeostasis [25–27]. Four classes of energy-dependent protease systems have been identified throughout prokaryotes: ClpAP/XP, ClpYQ (also named HslUV), FtsH and Lon. ClpP and ClpQ, the catalytic cores of the proteases, require Clp ATPase chaperones for the recognition and unfolding of substrates; on the other hand, in FtsH and Lon, a single polypeptide contains both ATPase and proteolytic activity [26, 28]. The ClpP protease and Clp ATPase, which are widely distributed and highly conserved in various bacteria species as well as mitochondria and chloroplasts of eukaryotic cells [27, 29, 30], have been demonstrated to function in the regulation of stress response, sporulation and cell division [31, 32].