Journal of Microbiology

Volume 61(3); March 2023

Editorial

Editorial] Bacterial Regulatory Mechanisms for the Control of Cellular Processes: Simple Organisms’ Complex Regulation: Jin-Won Lee; J. Microbiol. 2023;61(3):273-276. Published online April 3, 2023; DOI: https://doi.org/10.1007/s12275-023-00036-6

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Abstract: Bacteria employ a diverse array of cellular regulatory mechanisms to successfully adapt and thrive in ever-changing environments, including but not limited to temperature changes, fluctuations in nutrient availability, the presence or absence of electron acceptors such as oxygen, the availability of metal ions crucial for enzyme activity, and the existence of antibiotics. Bacteria can virtually modulate any step of gene expression from transcr!ptional initiation to posttranslational modification of a protein for the control of cellular processes. Furthermore, one gene regulator often controls another in a complex gene regulatory network. Thus, it is not easy to fully understand the intricacies of bacterial regulatory mechanisms in various environments. In this special issue, while acknowledging the challenge of covering all aspects of bacterial regulatory mechanisms across diverse environments, seven review articles are included to provide insight into the recent progress in understanding such mechanisms from different perspectives: positive regulatory mechanisms by secondary messenger (cAMP receptor protein), two-component signal transduction mechanisms (Rcs and Cpx), diverse regulatory mechanisms by a specific environmental factor in specific bacteria (oxygen availability in Mycobacterium and manganese ion availability in Salmonella), diverse regulatory mechanisms by a specific environmental factor (temperature and antibiotics), and regulatory mechanisms by antibiotics in cell wall synthesis. Bacteria, as ubiquitous organisms that can be found in almost every environment, carry out complex cellular processes that allow them to survive and thrive in a variety of different conditions despite their small size and relative simplicity. One of the key factors that allows bacteria to carry out these complex processes is their ability to regulate gene expression through various mechanisms. Gene expression is a fundamental biological process by which the genetic information encoded in a gene is transcribed into an RNA molecule and subsequently translated into a functional gene product, often a protein. Furthermore, the activity levels of proteins may further be altered by posttranslational modification. Regulation of gene expression refers to the control of the amount and timing of gene expression, and thus it can be divided into transcr!ptional, translational, and posttranslational levels.

Reviews

cAMP Activation of the cAMP Receptor Protein, a Model Bacterial Transcription Factor: Hwan Youn , Marcus Carranza; J. Microbiol. 2023;61(3):277-287. Published online March 9, 2023; DOI: https://doi.org/10.1007/s12275-023-00028-6

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Abstract: The active and inactive structures of the Escherichia coli cAMP receptor protein (CRP), a model bacterial transcr!ption factor, are compared to generate a paradigm in the cAMP-induced activation of CRP. The resulting paradigm is shown to be consistent with numerous biochemical studies of CRP and CRP*, a group of CRP mutants displaying cAMP-free activity. The cAMP affinity of CRP is dictated by two factors: (i) the effectiveness of the cAMP pocket and (ii) the protein equilibrium of apo-CRP. How these two factors interplay in determining the cAMP affinity and cAMP specificity of CRP and CRP* mutants are discussed. Both the current understanding and knowledge gaps of CRP-DNA interactions are also described. This review ends with a list of several important CRP issues that need to be addressed in the future.

Manganese Transporter Proteins in Salmonella enterica serovar Typhimurium: Nakyeong Ha , Eun-Jin Lee; J. Microbiol. 2023;61(3):289-296. Published online March 2, 2023; DOI: https://doi.org/10.1007/s12275-023-00027-7

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Abstract: The metal cofactors are essential for the function of many enzymes. The host restricts the metal acquisition of pathogens for their immunity and the pathogens have evolved many ways to obtain metal ions for their survival and growth. Salmonella enterica serovar Typhimurium also needs several metal cofactors for its survival, and manganese has been found to contribute to Salmonella pathogenesis. Manganese helps Salmonella withstand oxidative and nitrosative stresses. In addition, manganese affects glycolysis and the reductive TCA, which leads to the inhibition of energetic and biosynthetic metabolism. Therefore, manganese homeostasis is crucial for full virulence of Salmonella. Here, we summarize the current information about three importers and two exporters of manganese that have been identified in Salmonella. MntH, SitABCD, and ZupT have been shown to participate in manganese uptake. mntH and sitABCD are upregulated by low manganese concentration, oxidative stress, and host NRAMP1 level. mntH also contains a Mn2+- dependent riboswitch in its 5′ UTR. Regulation of zupT expression requires further investigation. MntP and YiiP have been identified as manganese efflux proteins. mntP is transcr!ptionally activated by MntR at high manganese levels and repressed its activity by MntS at low manganese levels. Regulation of yiiP requires further analysis, but it has been shown that yiiP expression is not dependent on MntS. Besides these five transporters, there might be additional transporters that need to be identified.

Mycobacterial Regulatory Systems Involved in the Regulation of Gene Expression Under Respiration‑Inhibitory Conditions: Yuna Oh , Ha-Na Lee , Eon-Min Ko , Ji-A Jeong , Sae Woong Park , Jeong-Il Oh; J. Microbiol. 2023;61(3):297-315. Published online February 27, 2023; DOI: https://doi.org/10.1007/s12275-023-00026-8

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Abstract: Mycobacterium tuberculosis is the causative agent of tuberculosis. M. tuberculosis can survive in a dormant state within the granuloma, avoiding the host-mounting immune attack. M. tuberculosis bacilli in this state show increased tolerance to antibiotics and stress conditions, and thus the transition of M. tuberculosis to the nonreplicating dormant state acts as an obstacle to tuberculosis treatment. M. tuberculosis in the granuloma encounters hostile environments such as hypoxia, nitric oxide, reactive oxygen species, low pH, and nutrient deprivation, etc., which are expected to inhibit respiration of M. tuberculosis. To adapt to and survive in respiration-inhibitory conditions, it is required for M. tuberculosis to reprogram its metabolism and physiology. In order to get clues to the mechanism underlying the entry of M. tuberculosis to the dormant state, it is important to understand the mycobacterial regulatory systems that are involved in the regulation of gene expression in response to respiration inhibition. In this review, we briefly summarize the information regarding the regulatory systems implicated in upregulation of gene expression in mycobacteria exposed to respiration-inhibitory conditions. The regulatory systems covered in this review encompass the DosSR (DevSR) two-component system, SigF partner switching system, MprBA-SigE-SigB signaling pathway, cAMP receptor protein, and stringent response.

Envelope‑Stress Sensing Mechanism of Rcs and Cpx Signaling Pathways in Gram‑Negative Bacteria: Seung-Hyun Cho , Kilian Dekoninck , Jean-Francois Collet; J. Microbiol. 2023;61(3):317-329. Published online March 9, 2023; DOI: https://doi.org/10.1007/s12275-023-00030-y

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Abstract: The global public health burden of bacterial antimicrobial resistance (AMR) is intensified by Gram-negative bacteria, which have an additional membrane, the outer membrane (OM), outside of the peptidoglycan (PG) cell wall. Bacterial twocomponent systems (TCSs) aid in maintaining envelope integrity through a phosphorylation cascade by controlling gene expression through sensor kinases and response regulators. In Escherichia coli, the major TCSs defending cells from envelope stress and adaptation are Rcs and Cpx, which are aided by OM lipoproteins RcsF and NlpE as sensors, respectively. In this review, we focus on these two OM sensors. β-Barrel assembly machinery (BAM) inserts transmembrane OM proteins (OMPs) into the OM. BAM co-assembles RcsF, the Rcs sensor, with OMPs, forming the RcsF-OMP complex. Researchers have presented two models for stress sensing in the Rcs pathway. The first model suggests that LPS perturbation stress disassembles the RcsF-OMP complex, freeing RcsF to activate Rcs. The second model proposes that BAM cannot assemble RcsF into OMPs when the OM or PG is under specific stresses, and thus, the unassembled RcsF activates Rcs. These two models may not be mutually exclusive. Here, we evaluate these two models critically in order to elucidate the stress sensing mechanism. NlpE, the Cpx sensor, has an N-terminal (NTD) and a C-terminal domain (CTD). A defect in lipoprotein trafficking
results
in NlpE retention in the inner membrane, provoking the Cpx response. Signaling requires the NlpE NTD, but not the NlpE CTD; however, OM-anchored NlpE senses adherence to a hydrophobic surface, with the NlpE CTD playing a key role in this function.

Membrane Proteins as a Regulator for Antibiotic Persistence in Gram‑Negative Bacteria: Jia Xin Yee , Juhyun Kim , Jinki Yeom; J. Microbiol. 2023;61(3):331-341. Published online February 17, 2023; DOI: https://doi.org/10.1007/s12275-023-00024-w

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Abstract: Antibiotic treatment failure threatens our ability to control bacterial infections that can cause chronic diseases. Persister bacteria are a subpopulation of physiological variants that becomes highly tolerant to antibiotics. Membrane proteins play crucial roles in all living organisms to regulate cellular physiology. Although a diverse membrane component involved in persistence can result in antibiotic treatment failure, the regulations of antibiotic persistence by membrane proteins has not been fully understood. In this review, we summarize the recent advances in our understanding with regards to membrane proteins in Gram-negative bacteria as a regulator for antibiotic persistence, highlighting various physiological mechanisms in bacteria.

Temperature Matters: Bacterial Response to Temperature Change: Seongjoon Moon , Soojeong Ham , Juwon Jeong , Heechan Ku , Hyunhee Kim , Changhan Lee; J. Microbiol. 2023;61(3):343-357. Published online April 3, 2023; DOI: https://doi.org/10.1007/s12275-023-00031-x

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Abstract: Temperature is one of the most important factors in all living organisms for survival. Being a unicellular organism, bacterium requires sensitive sensing and defense mechanisms to tolerate changes in temperature. During a temperature shift, the structure and composition of various cellular molecules including nucleic acids, proteins, and membranes are affected. In addition, numerous genes are induced during heat or cold shocks to overcome the cellular stresses, which are known as heat- and cold-shock proteins. In this review, we describe the cellular phenomena that occur with temperature change and bacterial responses from a molecular perspective, mainly in Escherichia coli.

Assembly of Bacterial Surface Glycopolymers as an Antibiotic Target: Hongbaek Cho; J. Microbiol. 2023;61(3):359-367. Published online March 23, 2023; DOI: https://doi.org/10.1007/s12275-023-00032-w

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Abstract: Bacterial cells are covered with various glycopolymers such as peptidoglycan (PG), lipopolysaccharides (LPS), teichoic acids, and capsules. Among these glycopolymers, PG assembly is the target of some of our most effective antibiotics, consistent with its essentiality and uniqueness to bacterial cells. Biosynthesis of other surface glycopolymers have also been acknowledged as potential targets for developing therapies to control bacterial infections, because of their importance for bacterial survival in the host environment. Moreover, biosynthesis of most surface glycopolymers are closely related to PG assembly because the same lipid carrier is shared for glycopolymer syntheses. In this review, I provide an overview of PG assembly and antibiotics that target this pathway. Then, I discuss the implications of a common lipid carrier being used for assembly of PG and other surface glycopolymers in antibiotic development.

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2023 Special Issue