scholarly journals The Epipeptide Biosynthesis Locus epeXEPAB Is Widely Distributed in Firmicutes and Triggers Intrinsic Cell Envelope Stress

2021 ◽  
pp. 1-12
Author(s):  
Philipp F. Popp ◽  
Lena Friebel ◽  
Alhosna Benjdia ◽  
Alain Guillot ◽  
Olivier Berteau ◽  
...  
Keyword(s):  
Stress Response ◽  
Stationary Phase ◽  
Cell Envelope ◽  
Biological Efficiency ◽  
Intrinsic Immunity ◽  
Global Regulators ◽  
Envelope Stress ◽  
Direct Binding ◽  
Transition State Regulator ◽  
Necessary And Sufficient

The <i>epeXEPAB</i> (formerly <i>yydFGHIJ</i>) locus of <i>Bacillus subtilis</i> encodes a minimalistic biosynthetic pathway for a linear antimicrobial epipeptide, EpeX, which is ribosomally produced and post-translationally processed by the action of the radical-SAM epimerase, EpeE, and a membrane-anchored signal 2 peptide peptidase, EpeP. The ABC transporter EpeAB provides intrinsic immunity against self-produced EpeX, without conferring resistance against extrinsically added EpeX. EpeX specifically targets, and severely perturbs the integrity of the cytoplasmic membrane, which leads to the induction of the Lia-dependent envelope stress response. Here, we provide new insights into the distribution, expression, and regulation of the minimalistic <i>epeXEPAB</i> locus of <i>B. subtilis</i>, as well as the biosynthesis and biological efficiency of the produced epipeptide EpeX*. A comprehensive comparative genomics study demonstrates that the <i>epe</i>-locus is restricted to but widely distributed within the phylum <i>Firmicutes</i>. The gene products of <i>epeXEP</i> are necessary and sufficient for the production of the mature antimicrobial peptide EpeX*. In <i>B. subtilis</i>, the <i>epeXEPAB</i> locus is transcribed from three different promoters, one upstream of <i>epeX</i> (P<sub><i>epeX</i></sub>) and two within <i>epeP</i> (P<sub><i>epeA1</i></sub> and P<sub><i>epeA2</i></sub>). While the latter two are mostly constitutive, P<sub><i>epeX</i></sub> shows a growth phase-dependent induction at the onset of stationary phase. We demonstrate that this regulation is the result of the antagonistic action of two global regulators: The transition state regulator AbrB keeps the <i>epe</i> locus shut off during exponential growth by direct binding. This tight repression is relieved by the master regulator of sporulation, Spo0A, which counteracts the AbrB-dependent repression of <i>epeXEPAB</i> expression during the transition to stationary phase. The net result of these three ­promoters is an expression pattern that ensures EpeAB-dependent autoimmunity prior to EpeX* production. In the absence of EpeAB, the general envelope stress response proteins LiaIH can compensate for the loss of specific autoimmunity by providing sufficient protection against the membrane-perturbating action of EpeX*. Hence, the transcriptional regulation of <i>epe</i> expression and the resulting intrinsic induction of the two corresponding resistance functions, encoded by <i>epeAB</i> and <i>liaIH</i>, are well balanced to provide a need-based immunity against mature EpeX*.

scholarly journals Phyletic distribution and diversification of the Phage Shock Protein stress response system in bacteria and archaea

2021 ◽  
Author(s):  
Philipp F. Popp ◽  
Vadim M. Gumerov ◽  
Ekaterina P. Andrianova ◽  
Lisa Bewersdorf ◽  
Thorsten Mascher ◽  
...  
Keyword(s):  
Stress Response ◽  
Large Scale ◽  
Cell Envelope ◽  
Model Organisms ◽  
Microbial World ◽  
Natural Classification ◽  
Response System ◽  
Core Proteins ◽  
Envelope Stress

AbstractThe bacterial cell envelope is an essential structure that protects the cell from environmental threats, while simultaneously serving as communication interface and diffusion barrier. Therefore, maintaining cell envelope integrity is of vital importance for all microorganisms. Not surprisingly, evolution has shaped conserved protection networks that connect stress perception, transmembrane signal transduction and mediation of cellular responses upon cell envelope stress. The phage shock protein (PSP) stress response is one of such conserved protection networks. Most of the knowledge about the Psp response comes from studies in the Gram-negative model bacterium, Escherichia coli where the Psp system consists of several well-defined protein components. Homologous systems were identified in representatives of Proteobacteria, Actinobacteria, and Firmicutes; however, the Psp system distribution in the microbial world remains largely unknown. By carrying out a large-scale, unbiased comparative genomics analysis, we found components of the Psp system in many bacterial and archaeal phyla and demonstrated that the PSP system deviates dramatically from the proteobacterial prototype. Two of its core proteins, PspA and PspC, have been integrated in various (often phylum-specifically) conserved protein networks during evolution. Based on protein sequence and gene neighborhood analyses of pspA and pspC homologs, we built a natural classification system of PSP networks in bacteria and archaea. We performed a comprehensive in vivo protein interaction screen for the PSP network newly identified in the Gram-positive model organism Bacillus subtilis and found a strong interconnected PSP response system, illustrating the validity of our approach. Our study highlights the diversity of PSP organization and function across many bacterial and archaeal phyla and will serve as foundation for future studies of this envelope stress response beyond model organisms.

scholarly journals The Rcs System in Enterobacteriaceae: Envelope Stress Responses and Virulence Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiao Meng ◽  
Glenn Young ◽  
Jingyu Chen
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Cell Envelope ◽  
Regulatory System ◽  
Virulence Regulation ◽  
Bacterial Interaction ◽  
Envelope Stress

The bacterial cell envelope is a protective barrier at the frontline of bacterial interaction with the environment, and its integrity is regulated by various stress response systems. The Rcs (regulator of capsule synthesis) system, a non-orthodox two-component regulatory system (TCS) found in many members of the Enterobacteriaceae family, is one of the envelope stress response pathways. The Rcs system can sense envelope damage or defects and regulate the transcriptome to counteract stress, which is particularly important for the survival and virulence of pathogenic bacteria. In this review, we summarize the roles of the Rcs system in envelope stress responses (ESRs) and virulence regulation. We discuss the environmental and intrinsic sources of envelope stress that cause activation of the Rcs system with an emphasis on the role of RcsF in detection of envelope stress and signal transduction. Finally, the different regulation mechanisms governing the Rcs system’s control of virulence in several common pathogens are introduced. This review highlights the important role of the Rcs system in the environmental adaptation of bacteria and provides a theoretical basis for the development of new strategies for control, prevention, and treatment of bacterial infections.

scholarly journals The three-component system EsrISR regulates a cell envelope stress response inCorynebacterium glutamicum

2017 ◽  
Vol 106 (5) ◽  
pp. 719-741 ◽  
Author(s):  
Britta Kleine ◽  
Ava Chattopadhyay ◽  
Tino Polen ◽  
Daniela Pinto ◽  
Thorsten Mascher ◽  
...  
Keyword(s):  
Stress Response ◽  
Cell Envelope ◽  
Component System ◽  
Envelope Stress ◽  
A Cell

scholarly journals The Cell Envelope Stress Response of Bacillus subtilis towards Laspartomycin C

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 729
Author(s):  
Angelika Diehl ◽  
Thomas M. Wood ◽  
Susanne Gebhard ◽  
Nathaniel I. Martin ◽  
Georg Fritz
Keyword(s):  
Cell Wall ◽  
Bacillus Subtilis ◽  
Stress Response ◽  
Cell Envelope ◽  
Resistance Mechanisms ◽  
Detailed Knowledge ◽  
Knock Out ◽  
Lipid Ii ◽  
Envelope Stress ◽  
The Impact

Cell wall antibiotics are important tools in our fight against Gram-positive pathogens, but many strains become increasingly resistant against existing drugs. Laspartomycin C is a novel antibiotic that targets undecaprenyl phosphate (UP), a key intermediate in the lipid II cycle of cell wall biosynthesis. While laspartomycin C has been thoroughly examined biochemically, detailed knowledge about potential resistance mechanisms in bacteria is lacking. Here, we use reporter strains to monitor the activity of central resistance modules in the Bacillus subtilis cell envelope stress response network during laspartomycin C attack and determine the impact on the resistance of these modules using knock-out strains. In contrast to the closely related UP-binding antibiotic friulimicin B, which only activates ECF σ factor-controlled stress response modules, we find that laspartomycin C additionally triggers activation of stress response systems reacting to membrane perturbation and blockage of other lipid II cycle intermediates. Interestingly, none of the studied resistance genes conferred any kind of protection against laspartomycin C. While this appears promising for therapeutic use of laspartomycin C, it raises concerns that existing cell envelope stress response networks may already be poised for spontaneous development of resistance during prolonged or repeated exposure to this new antibiotic.

scholarly journals Rcs Phosphorelay Responses to Truncated Lipopolysaccharide-Induced Cell Envelope Stress in Yersinia enterocolitica

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5718
Author(s):  
Jiao Meng ◽  
Junhong Xu ◽  
Can Huang ◽  
Jingyu Chen
Keyword(s):  
Stress Response ◽  
Outer Membrane ◽  
Yersinia Enterocolitica ◽  
Antimicrobial Agents ◽  
Cell Envelope ◽  
Sodium Dodecyl ◽  
Cell Surface Hydrophobicity ◽  
Membrane Function ◽  
Cell Functions ◽  
Envelope Stress

Lipopolysaccharide (LPS) is the major component of the outer membrane of Gram-negative bacteria, and its integrity is monitored by various stress response systems. Although the Rcs system is involved in the envelope stress response and regulates genes controlling numerous bacterial cell functions of Yersinia enterocolitica, whether it can sense the truncated LPS in Y. enterocolitica remains unclear. In this study, the deletion of the Y. enterocolitica waaF gene truncated the structure of LPS and produced a deep rough LPS. The truncated LPS increased the cell surface hydrophobicity and outer membrane permeability, generating cell envelope stress. The truncated LPS also directly exposed the smooth outer membrane to the external environment and attenuated the resistance to adverse conditions, such as impaired survival under polymyxin B and sodium dodecyl sulfate (SDS) exposure. Further phenotypic experiment and gene expression analysis indicated that the truncated LPS was correlated with the activation of the Rcs phosphorelay, thereby repressing cell motility and biofilm formation. Our findings highlight the importance of LPS integrity in maintaining membrane function and broaden the understanding of Rcs phosphorelay signaling in response to cell envelope stress, thus opening new avenues to develop effective antimicrobial agents for combating Y. enterocolitica infections.

scholarly journals Lon Protease Influences Antibiotic Production and UV Tolerance of Pseudomonas fluorescens Pf-5

2000 ◽  
Vol 66 (7) ◽  
pp. 2718-2725 ◽  
Author(s):  
Cheryl A. Whistler ◽  
Virginia O. Stockwell ◽  
Joyce E. Loper
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Stationary Phase ◽  
Pseudomonas Fluorescens ◽  
Sigma Factor ◽  
Plant Pathogens ◽  
Antibiotic Production ◽  
Disease Suppression ◽  
Global Regulator ◽  
Global Regulators

ABSTRACT Pseudomonas fluorescens Pf-5 is a soil bacterium that suppresses plant pathogens due in part to its production of the antibiotic pyoluteorin. Previous characterization of Pf-5 revealed three global regulators, including the stationary-phase sigma factor ςS and the two-component regulators GacA and GacS, that influence both antibiotic production and stress response. In this report, we describe the serine protease Lon as a fourth global regulator influencing these phenotypes in Pf-5. lon mutants overproduced pyoluteorin, transcribed pyoluteorin biosynthesis genes at enhanced levels, and were more sensitive to UV exposure than Pf-5. Thelon gene was preceded by sequences that resembled promoters recognized by the heat shock sigma factor ς32(ςH) of Escherichia coli, and Lon accumulation by Pf-5 increased after heat shock. Therefore, ςH represents the third sigma factor (with ςS and ς70) implicated in the regulation of antibiotic production by P. fluorescens. Lon protein levels were similar in stationary-phase and exponentially growing cultures of Pf-5 and were not positively affected by the global regulator ςS or GacS. The association of antibiotic production and stress response has practical implications for the success of disease suppression in the soil environment, where biological control organisms such as Pf-5 are likely to encounter environmental stresses.

scholarly journals A Cytosine Methytransferase Modulates the Cell Envelope Stress Response in the Cholera Pathogen

PLoS Genetics ◽  
2015 ◽  
Vol 11 (11) ◽  
pp. e1005666 ◽  
Author(s):  
Michael C. Chao ◽  
Shijia Zhu ◽  
Satoshi Kimura ◽  
Brigid M. Davis ◽  
Eric E. Schadt ◽  
...  
Keyword(s):  
Stress Response ◽  
Cell Envelope ◽  
Envelope Stress

scholarly journals Role ofBordetella pertussisRseA in the cell envelope stress response and adenylate cyclase toxin release

2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Tomoko Hanawa ◽  
Hideo Yonezawa ◽  
Hayato Kawakami ◽  
Shigeru Kamiya ◽  
Sandra K. Armstrong
Keyword(s):  
Stress Response ◽  
Adenylate Cyclase ◽  
Cell Envelope ◽  
Envelope Stress ◽  
Adenylate Cyclase Toxin
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