The RpfC (Rv1884) atomic structure shows high structural conservation within the resuscitation-promoting factor catalytic domain

Chauviac, F.X.; Robertson, Giles; Quay, Doris H.X.; Bagnéris, Claire; Dumas, Christian; Henderson, Brian E.; Ward, John M.; Keep, Nicholas H.; Cohen‐Gonsaud, Martin

doi:10.1107/s2053230x1401317x

Cited by 14 publications

(10 citation statements)

References 34 publications

(38 reference statements)

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“…Thus M. tuberculosis has five homologues 222 – 224 . Rpfs can have peptidoglycanase and muralytic activity 225 – 230 and known crystal structures are consistent with this 231 – 236 . These activities can certainly account for at least some 237 of the resuscitation-promoting properties.…”

Section: Pheromonal Proteinssupporting

confidence: 54%

Individuality, phenotypic differentiation, dormancy and ‘persistence’ in culturable bacterial systems: commonalities shared by environmental, laboratory, and clinical microbiology

2015

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For bacteria, replication mainly involves growth by binary fission. However, in a very great many natural environments there are examples of phenotypically dormant, non-growing cells that do not replicate immediately and that are phenotypically ‘nonculturable’ on media that normally admit their growth. They thereby evade detection by conventional culture-based methods. Such dormant cells may also be observed in laboratory cultures and in clinical microbiology. They are usually more tolerant to stresses such as antibiotics, and in clinical microbiology they are typically referred to as ‘persisters’. Bacterial cultures necessarily share a great deal of relatedness, and inclusive fitness theory implies that there are conceptual evolutionary advantages in trading a variation in growth rate against its mean, equivalent to hedging one’s bets. There is much evidence that bacteria exploit this strategy widely. We here bring together data that show the commonality of these phenomena across environmental, laboratory and clinical microbiology. Considerable evidence, using methods similar to those common in environmental microbiology, now suggests that many supposedly non-communicable, chronic and inflammatory diseases are exacerbated (if not indeed largely caused) by the presence of dormant or persistent bacteria (the ability of whose components to cause inflammation is well known). This dormancy (and resuscitation therefrom) often reflects the extent of the availability of free iron. Together, these phenomena can provide a ready explanation for the continuing inflammation common to such chronic diseases and its correlation with iron dysregulation. This implies that measures designed to assess and to inhibit or remove such organisms (or their access to iron) might be of much therapeutic benefit.

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Section: Pheromonal Proteinssupporting

confidence: 54%

Individuality, phenotypic differentiation, dormancy and ‘persistence’ in culturable bacterial systems: commonalities shared by environmental, laboratory, and clinical microbiology

2015

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“…SpsB group are the proteins that resemble RpfB in ancillary domain structure. YuiC is a member of the SpsC group which, like RpfC [ 15 ], RpfD and RpfE, only has a signal peptide and short extensions beyond the conserved catalytic domain. The SpsD group contains a COG3883 domain, only found in putative peptidoglycan cleaving enzymes in Firmicutes, in addition to the catalytic domain.…”

Section: Introductionmentioning

confidence: 99%

Structure of the stationary phase survival protein YuiC from B.subtilis

et al. 2015

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BackgroundStationary phase survival proteins (Sps) were found in Firmicutes as having analogous domain compositions, and in some cases genome context, as the resuscitation promoting factors of Actinobacteria, but with a different putative peptidoglycan cleaving domain.ResultsThe first structure of a Firmicute Sps protein YuiC from B. subtilis, is found to be a stripped down version of the cell-wall peptidoglycan hydrolase MltA. The YuiC structures are of a domain swapped dimer, although some monomer is also found in solution. The protein crystallised in the presence of pentasaccharide shows a 1,6-anhydrodisaccharide sugar product, indicating that YuiC cleaves the sugar backbone to form an anhydro product at least on lengthy incubation during crystallisation.ConclusionsThe structural simplification of MltA in Sps proteins is analogous to that of the resuscitation promoting factor domains of Actinobacteria, which are stripped down versions of lysozyme and soluble lytic transglycosylase proteins.Electronic supplementary materialThe online version of this article (doi:10.1186/s12900-015-0039-z) contains supplementary material, which is available to authorized users.

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“…Using in silico analysis to identify possible differences in biological function, we noted some interesting variations. Crystal/nuclear magnetic resonance (NMR) structures of RpfB in M. tuberculosis (RpfB Mtb ) (21,22), RpfC Mtb (23), and RpfE Mtb (24) have been determined and confirm that all three share the same critical amino acids and catalytic domain organization. RpfC Mtb retains two lysine residues at positions 26 and 33, and the variation in amino acid composition at these positions results in different charge distributions around the ligand-binding pocket for the individual Rpfs, which has been postulated to lead to substrate specificity (23).…”

Section: Resultsmentioning

confidence: 87%

“…The Lys26 residue in RpfC Mtb is replaced with a Tyr in RpfA Mtb , RpfB Mtb , and RpfE Mtb (Fig. S1A) and with a Leu in RpfD Mtb (23). In contrast, the four Rpfs in M. smegmatis display greater variation in amino acid composition at this position, with Tyr in RpfA in M. smegmatis (RpfA Msm ) and RpfE Msm , Phe in RpfB Msm , and His in RpfE2 Msm (Fig.…”

Section: Resultsmentioning

confidence: 99%

Resuscitation-Promoting Factors Are Required for Mycobacterium smegmatis Biofilm Formation

Ealand

Rimal

Chang

et al. 2018

Appl Environ Microbiol

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Resuscitation-promoting factors (Rpfs) have previously been shown to act as growth-stimulatory molecules via their lysozyme-like activity on peptidoglycan in the bacterial cell wall. In this study, we investigated the ability of strains lacking genes to form biofilms and tested their susceptibilities to cell wall-targeting agents. contains four distinct homologues, namely, MSMEG_5700 (), MSMEG_5439 (), MSMEG_4640 (), and MSMEG_4643 (). During axenic growth of the wild-type strain, all four mRNA transcripts were expressed to various degrees, but the expression of MSMEG_4643 was significantly greater during exponential growth. Similarly, all mRNA transcripts could be detected in biofilms grown for 7, 14, and 28 days, with MSMEG_4643 expressed at the highest abundance after 7 days. In-frame unmarked deletion mutants (single and combinatorial) were generated and displayed altered colony morphologies and the inability to form typical biofilms. Moreover, any strain lacking and simultaneously exhibited increased susceptibility to rifampin, vancomycin, and SDS. Exogenous Rpf supplementation in the form of culture filtrate failed to restore biofilm formation. Liquid chromatography-mass spectrometry (LC-MS) analysis of peptidoglycan (PG) suggested a reduction in 4-3 cross-linked PG in the Δ mutant strain. In addition, the level of PG-repeat units terminating in 1,6-anhydroMurNAc appeared to be significantly reduced in the quadruple mutant. Collectively, our data have shown that Rpfs play an important role in biofilm formation, possibly through alterations in PG cross-linking and the production of signaling molecules. The cell wall of pathogenic mycobacteria is composed of peptidoglycan, arabinogalactan, mycolic acids, and an outer capsule. This inherent complexity renders it resistant to many antibiotics. Consequently, its biosynthesis and remodeling during growth directly impact viability. Resuscitation-promoting factors (Rpfs), enzymes with lytic transglycosylase activity, have been associated with the revival of dormant cells and subsequent resumption of vegetative growth. , a soil saprophyte and close relative of the human pathogen, encodes four distinct Rpfs. Herein, we assessed the relationship between Rpfs and biofilm formation, which is used as a model to study drug tolerance and bacterial signaling in mycobacteria. We demonstrated that progressive deletion of genes hampered the development of biofilms and reduced drug tolerance. These effects were accompanied by a reduction in muropeptide production and altered peptidoglycan cross-linking. Collectively, these observations point to an important role for Rpfs in mycobacterial communication and drug tolerance.

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The RpfC (Rv1884) atomic structure shows high structural conservation within the resuscitation-promoting factor catalytic domain

Cited by 14 publications

References 34 publications

Individuality, phenotypic differentiation, dormancy and ‘persistence’ in culturable bacterial systems: commonalities shared by environmental, laboratory, and clinical microbiology

Individuality, phenotypic differentiation, dormancy and ‘persistence’ in culturable bacterial systems: commonalities shared by environmental, laboratory, and clinical microbiology

Structure of the stationary phase survival protein YuiC from B.subtilis

Resuscitation-Promoting Factors Are Required for Mycobacterium smegmatis Biofilm Formation

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