Two-Component Signal Transduction Systems That Regulate the Temporal and Spatial Expression of Myxococcus xanthus Sporulation Genes

Sarwar, Zaara; Garza, Anthony G.

doi:10.1128/jb.00474-15

Cited by 13 publications

(22 citation statements)

References 95 publications

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“…Previous work indicated that the Nla28 EBP is a response regulator that forms a two component signal transduction system with the membrane-bound histidine kinase sensor Nla28S 47,48 .…”

Section: Discussionmentioning

confidence: 99%

The σ54 System Directly Regulates Bacterial Natural Product Genes

Welch

Garza

2020

Preprint

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Bacterial-derived polyketide and non-ribosomal peptide natural products are crucial sources of therapeutic agents and yet little is known about the conditions that favor activation of natural product genes or the regulatory machinery that controls their transcription. Recent findings suggest that the σ54 system, which includes σ54-loaded RNA polymerase and transcriptional activators called enhancer binding proteins (EBPs), might be a common regulator of natural product genes. Here, we explore this idea by analyzing four putative σ54 promoters identified in the sequences of Myxococcus xanthus natural product gene clusters. We show that mutations in the putative σ54-RNA polymerase binding regions reduce in vivo promoter activities during growth and development. We also show that the EBP Nla28 is important for the in vivo activities of three natural product promoters, that Nla28 binds to wild-type fragments of these promoters in vitro, and that in vitro binding is lost when the putative Nla28 binding sites are mutated. These results indicate that the natural product promoters are bona fide σ54 promoter elements and three are direct targets of Nla28. Interestingly, the vast majority of experimentally confirmed and putative σ54 promoters in M. xanthus natural product clusters are located within genes and not in intergenic sequences.

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“…Previous work indicated that the Nla28 EBP is a response regulator that forms a two component signal transduction system with the membrane-bound histidine kinase sensor Nla28S 47,48 .…”

Section: Discussionmentioning

confidence: 99%

The σ54 System Directly Regulates Bacterial Natural Product Genes

Welch

Garza

2020

Preprint

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“…xanthus NtrC-like RRs are known to regulate such complex behaviors as multicellular fruiting body formation, sporulation, T4P-dependent social motility, and predation [ 3 , 25 , 26 , 29 , 30 , 32 , 33 , 35 , 36 , 55 ]. There is also evidence that there are hierarchal and/or overlapping transcriptional programs mediated by these complex TCS networks [ 3 , 33 ]. Therefore, M .…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, several NtrC-like RRs and related proteins collectively described as NtrC-like activators (Nla) are known to coordinate development and motility of M . xanthus [ 3 , 25 , 26 , 28 – 36 ]. Consistent with the paradigm that TCS maintain signaling fidelity at the biochemical level, broad cross-phosphorylation ("cross talk") between these systems does not seem to occur in M .…”

Section: Introductionmentioning

confidence: 99%

Suppressor mutations reveal an NtrC-like response regulator, NmpR, for modulation of Type-IV Pili-dependent motility in Myxococcus xanthus

et al. 2018

PLoS Genet

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Two-component signaling systems (TCS) regulate bacterial responses to environmental signals through the process of protein phosphorylation. Specifically, sensor histidine kinases (SK) recognize signals and propagate the response via phosphorylation of a cognate response regulator (RR) that functions to initiate transcription of specific genes. Signaling within a single TCS is remarkably specific and cross-talk between TCS is limited. However, regulation of the flow of information through complex signaling networks that include closely related TCS remains largely unknown. Additionally, many bacteria utilize multi-component signaling networks which provide additional genetic and biochemical interactions that must be regulated for signaling fidelity, input and output specificity, and phosphorylation kinetics. Here we describe the characterization of an NtrC-like RR that participates in regulation of Type-IV pilus-dependent motility of Myxococcus xanthus and is thus named NmpR, NtrC Modulator of Pili Regulator. A complex multi-component signaling system including NmpR was revealed by suppressor mutations that restored motility to cells lacking PilR, an evolutionarily conserved RR required for expression of pilA encoding the major Type-IV pilus monomer found in many bacterial species. The system contains at least four signaling proteins: a SK with a protoglobin sensor domain (NmpU), a hybrid SK (NmpS), a phospho-sink protein (NmpT), and an NtrC-like RR (NmpR). We demonstrate that ΔpilR bypass suppressor mutations affect regulation of the NmpRSTU multi-component system, such that NmpR activation is capable of restoring expression of pilA in the absence of PilR. Our findings indicate that pilus gene expression in M. xanthus is regulated by an extended network of TCS which interact to refine control of pilus function.

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“…Two-component systems are widely used by bacteria to sense and respond to their environments [21, 23, 35–40]. Although much work has been done to understand the cellular targets of TCSs, the signals that activate these TCSs remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

MifS, a DctB family histidine kinase, is a specific regulator of α-ketoglutarate response in Pseudomonas aeruginosa PAO1

et al. 2020

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The C5-dicarboxylate α-ketoglutarate (α-KG) is a preferred nutrient source for the opportunistic pathogen Pseudomonas aeruginosa . However, very little is known about how P. aeruginosa detects and responds to α-KG in the environment. Our laboratory has previously shown that the MifS/MifR two-component signal transduction system regulates α-KG assimilation in P. aeruginosa PAO1. In an effort to better understand how this bacterium detects α-KG, we characterized the MifS sensor histidine kinase. In this study we show that although MifS is a homologue of the C4-dicarboxylate sensor DctB, it specifically responds to the C5-dicarboxylate α-KG. MifS activity increased >10-fold in the presence of α-KG, while the related C5-dicarboxylate glutarate caused only a 2-fold increase in activity. All other dicarboxylates tested did not show any significant effect on MifS activity. Homology modelling of the MifS sensor domain revealed a substrate binding pocket for α-KG. Using protein modelling and mutational analysis, we identified nine residues that are important for α-KG response, including one residue that determines the substrate specificity of MifS. Further, we found that MifS has a novel cytoplasmic linker domain that is required for α-KG response and is probably involved in signal transduction from the sensor domain to the cytoplasmic transmitter domain. Until this study, DctB family histidine kinases were known to only respond to C4-dicarboxylates. Our work shows that MifS is a novel member of the DctB family histidine kinase that specifically responds to α-KG.

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Two-Component Signal Transduction Systems That Regulate the Temporal and Spatial Expression of Myxococcus xanthus Sporulation Genes

Cited by 13 publications

References 95 publications

The σ54 System Directly Regulates Bacterial Natural Product Genes

The σ54 System Directly Regulates Bacterial Natural Product Genes

Suppressor mutations reveal an NtrC-like response regulator, NmpR, for modulation of Type-IV Pili-dependent motility in Myxococcus xanthus

MifS, a DctB family histidine kinase, is a specific regulator of α-ketoglutarate response in Pseudomonas aeruginosa PAO1

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