A Eukaryotic-like Ser/Thr Kinase Signals Bacteria to Exit Dormancy in Response to Peptidoglycan Fragments

Shah, Ishita M.; Laaberki, Maria-Halima; Popham, David L.; Dworkin, Jonathan

doi:10.1016/j.cell.2008.08.039

Cited by 440 publications

(549 citation statements)

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“…In conclusion, our study establishes a clear correlation between reversible protein phosphorylation by the PrkC/PrpC pair and gliding motility in M. pneumoniae but does not assert that protein phosphorylation by PrkC drives the gliding motor. Rather, we suggest that PrpC and PrkC constitute part of a regulatory circuit comparable to that in B. subtilis wherein the phosphorylation of elongation factor Tu and other phosphoproteins influences aspects of sporulation and cell wall biosynthesis (18,20). Homologous eSTP/eSTK-associated regulation of swarming in Myxococcus xanthus, cell division in Mycobacterium tuberculosis, and virulence in Yersinia pseudotuberculosis have been previously reported (19), indicating that reversible protein phosphorylation is coupled to a diverse slate of functions in bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…PrpC and its homologs are often partnered with the cognate kinase PrkC, a highly conserved eukaryotic-like Ser/Thr kinase (eSTK). Mutant analysis in Bacillus subtilis has shown that homologs to these enzymes regulate sporulation and cell wall development by reversible phosphorylation (18)(19)(20). Similar reversible phosphorylation might occur in M. pneumoniae, where terminal organelle proteins HMW1 and HMW2 (MPN310) are phosphorylated in an ATP-dependent manner (21).…”

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Protein Kinase/Phosphatase Function Correlates with Gliding Motility in Mycoplasma pneumoniae

Page

Krause

2013

J Bacteriol

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Mycoplasma pneumoniae exhibits a novel form of gliding motility that is mediated by the terminal organelle, a differentiated polar structure. Given that genes known to be involved in gliding in other organisms are absent in M. pneumoniae, random transposon mutagenesis was employed to generate mutants with gliding-deficient phenotypes. Transposon insertions in the only annotated Ser/Thr protein kinase gene (prkC; MPN248) and its cognate phosphatase gene (prpC; MPN247) in M. pneumoniae resulted in significant and contrasting effects on gliding frequencies. prkC mutant cells glided at approximately half the frequency of wild-type cells, while prpC mutant cells glided more than twice as frequently as wild-type cells. Phosphoprotein staining confirmed the association between phosphorylation of the cytoskeletal proteins HMW1 and HMW2 and membrane protein P1 and the gliding phenotype. When the prpC mutant was complemented by transposon delivery of a wild-type copy of the prpC allele, gliding frequencies and phosphorylation levels returned to the wild-type standard. Surprisingly, delivery of the recombinant wild-type prkC allele dramatically increased gliding frequency to a level approximately 3-fold greater than that of wild-type in the prkC mutant. Collectively, these data suggest that PrkC and PrpC work in opposition in M. pneumoniae to influence gliding frequency.M ycoplasma pneumoniae is a cell wall-less bacterial pathogen of the human respiratory tract causing primary atypical pneumonia and tracheobronchitis (1). Mycoplasmas lack major biosynthetic pathways, classical transcriptional regulators, chemotactic and other two-component systems, and the prototypical prokaryotic cell division apparatus (2, 3). The limited biosynthetic capabilities of mycoplasmas are generally explained by their evolution as obligate parasites of diverse eukaryotic hosts (4). Colonization of the host respiratory epithelium by M. pneumoniae requires gliding motility (5), which might facilitate access to receptors on the host cell surface and subsequent lateral spread.The gliding apparatus of M. pneumoniae is a polar terminal structure (6) that also functions in cell division (7) and adhesion to host receptors (2, 5). While the cytoskeletal protein HMW1 (MPN447) and membrane proteins P1, B/C, and P30 (MPN141, MPN142, and MPN453, respectively) localize to the terminal organelle and are required for gliding (5,(8)(9)(10), these proteins are also essential for cytadherence and attachment to surfaces. Accordingly, their distinct functions in gliding motility are difficult to define by mutagenesis alone. Given that the M. pneumoniae genome exhibits no homology to elements of defined gliding mechanisms (2, 3), including those of other gliding mycoplasmas (11-14), it was necessary to perform saturating transposon mutagenesis in order to identify the components specific to gliding (15). Transposon insertions in the genes encoding the cytoskeletal proteins P41 and P65 (MPN311 and MPN309, respectively) (16), which are known to localize to the termina...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Protein Kinase/Phosphatase Function Correlates with Gliding Motility in Mycoplasma pneumoniae

Page

Krause

2013

J Bacteriol

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“…Multiple reports show that STKs carrying PASTA domains play important regulatory roles in Mycobacterium and Corynebacterium. PASTA domains are known to bind peptidoglycan components and β-lactam antibiotics (21,32), and actinobacterial STKs carrying such domains (PknA and PknB) have been reported to phosphorylate several proteins involved in cell wall growth and cell division, including the mycobacterial DivIVA-orthologue Wag31 (e.g., refs. 24, 33-35).…”

Section: Diviva Phosphorylation Increases Dramatically When Cell Wallmentioning

confidence: 99%

“…20). For example, in B. subtilis, the STK PrkC controls germination of spores in response to muropeptides released from bacterial cell walls, and, in Streptococcus pneumoniae, the STK StkP is involved in coordination of growth and cell division (21,22). These two bacterial species have only two and one STKs, respectively, but the phylogenetic distribution of STKs among bacterial taxa is uneven; some groups encode only a few per genome whereas others have dozens-or, in some cases, even hundreds-of STK genes (23).…”

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The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria Streptomyces

Hempel

Cantlay

Molle

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

108

155

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In cells that exhibit apical growth, mechanisms that regulate cell polarity are crucial for determination of cellular shape and for the adaptation of growth to intrinsic and extrinsic cues. Broadly conserved pathways control cell polarity in eukaryotes, but less is known about polarly growing prokaryotes. An evolutionarily ancient form of apical growth is found in the filamentous bacteria Streptomyces, and is directed by a polarisome-like complex involving the essential protein DivIVA. We report here that this bacterial polarization machinery is regulated by a eukaryotic-type Ser/Thr protein kinase, AfsK, which localizes to hyphal tips and phosphorylates DivIVA. During normal growth, AfsK regulates hyphal branching by modulating branch-site selection and some aspect of the underlying polarisome-splitting mechanism that controls branching of Streptomyces hyphae. Further, AfsK is activated by signals generated by the arrest of cell wall synthesis and directly communicates this to the polarisome by hyperphosphorylating DivIVA. Induction of high levels of DivIVA phosphorylation by using a constitutively active mutant AfsK causes disassembly of apical polarisomes, followed by establishment of multiple hyphal branches elsewhere in the cell, revealing a profound impact of this kinase on growth polarity. The function of AfsK is reminiscent of the phoshorylation of polarity proteins and polarisome components by Ser/Thr protein kinases in eukaryotes.hyphal growth | protein phosphorylation | peptidoglycan | cytoskeleton | tip extension

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“…Nevertheless, these A third type of molecule that can trigger spore germination is low-molecular-weight fragments of growing cell peptidoglycan (PG). These PG fragments trigger spore germination by activating the protein kinase PrkC (30,32). While spore PG differs in structure from growing cell PG, and thus cortical PG fragments might not activate PrkC, it still seemed worth examining whether this mechanism was responsible for spore-tospore communication during spore germination.…”

Section: Resultsmentioning

confidence: 99%

Quantitative Analysis of Spatial-Temporal Correlations during Germination of Spores of Bacillus Species

et al. 2011

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Bacteria of Bacillus species sporulate upon starvation, and the resultant dormant spores germinate when the environment appears likely to allow the resumption of vegetative growth. Normally, the rates of germination of individual spores in populations are very heterogeneous, and the current work has investigated whether spore-to-spore communication enhances the synchronicity of germination. In order to do this work, time-lapse optical images of thousands of individual spores were captured during germination, and an image analysis algorithm was developed to do the following: (i) measure the positions and germination rates of many thousands of individual spores and (ii) compute pairwise correlations of their germination. This analysis showed that an individual spore's germination rate was dependent on its distance from other spores, especially at short distances. Thus, spores that were within a few micrometers exhibited an increased synchronicity in germination, suggesting that there is a mechanism for short-range communication between such spores during germination. However, two molecules known to be germinants that are released during germination, L-alanine and the 1:1 chelate of Ca 2؉ and dipicolinic acid, did not mediate spore-to-spore communication during germination.Bacteria of Bacillus species form spores in order to survive adverse environmental conditions (18, 28). These spores are metabolically dormant and highly resistant to most antibacterial agents. However, the dormant spores continually monitor their environment and can resume vegetative growth once the environment becomes suitable. The first step in a spore's return to growth is germination, which can be initiated by some specific nutrient germinant molecules, including amino acids, nucleosides, and sugars (16,27). A key early step in germination is the release of the spores' large pool (ϳ20% of the dry weight of spores' central region or core) of dipicolinic acid (DPA) that is chelated to divalent metal ions, predominantly Ca 2ϩ (Ca-DPA) (12,25,27). Recent studies with individual spores have shown that once rapid release of Ca-DPA during germination has begun, it is completed in only a few minutes (4,13,22,27,35). However, there are generally long lag times (t lag ) between the time of addition of a nutrient germinant to the initiation of rapid Ca-DPA release for individual spores, and t lag values vary greatly from spore to spore even in genetically identical populations germinating under the same conditions (4, 35). In contrast, the time needed for release of ϳ90% of a spore's Ca-DPA during germination is relatively constant at several minutes.The precise kinetics of spore germination are of great interest to the food and medical products industries, because once spores have germinated they are much easier to kill than the more resistant dormant spores. Unfortunately, the rates of germination of individual spores are extremely heterogeneous due to the variations in t lag (4,11,13,35). Some of the factors that influence t lag values have recently...

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A Eukaryotic-like Ser/Thr Kinase Signals Bacteria to Exit Dormancy in Response to Peptidoglycan Fragments

Cited by 440 publications

References 50 publications

Protein Kinase/Phosphatase Function Correlates with Gliding Motility in Mycoplasma pneumoniae

Protein Kinase/Phosphatase Function Correlates with Gliding Motility in Mycoplasma pneumoniae

The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria Streptomyces

Quantitative Analysis of Spatial-Temporal Correlations during Germination of Spores of Bacillus Species

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