Journal of Microbiology

Reviews

Proteostasis-targeted antibacterial strategies: Yoon Chae Jeong, Seong-Hyeon Kim, Seongjoon Moon, Hyunhee Kim, Changhan Lee; Received November 6, 2025 Accepted November 26, 2025 Published online February 12, 2026; DOI: https://doi.org/10.71150/jm.2511007 [Epub ahead of print]

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Abstract PDF: Protein quality control systems are increasingly recognized as a critical determinant of bacterial survival and antibiotic tolerance. Conventional antibiotics predominantly target nucleic acids, protein synthesis, or cell wall synthesis, yet bacterial adaptation and resistance emergence remain major challenges. Targeting the bacterial protein quality control machineries including molecular chaperones and proteases offers a promising strategy to overcome these limitations. Recent advances include small molecules and adaptor/degron mimetics that modulate the activities of chaperones and proteases, aggregation-prone peptides (APPs) that induce proteotoxic stress, and bacterial PROTAC (BacPROTAC) strategies that redirect endogenous proteases. Notably, persister and viable-but-non-culturable (VBNC) cells, which tolerate conventional antibiotics, remain susceptible to proteostasis-targeted approaches, thereby enabling killing in both actively dividing and dormant populations. Furthermore, synergistic strategies combining chaperone inhibition or protease activation with conventional antibiotics enhance bactericidal efficacy, suggesting a potential avenue to mitigate antimicrobial resistance. This review summarizes the mechanistic basis, recent developments, and translational potential of proteostasis-centered antibacterial strategies.

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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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.

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[Minireview]Cytoplasmic molecular chaperones in Pseudomonas species: Hyunhee Kim , Seongjoon Moon , Soojeong Ham , Kihyun Lee , Ute Römling , Changhan Lee; J. Microbiol. 2022;60(11):1049-1060. Published online November 1, 2022; DOI: https://doi.org/10.1007/s12275-022-2425-0

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Abstract PDF

Pseudomonas is widespread in various environmental and host niches. To promote rejuvenation, cellular protein homeostasis must be finely tuned in response to diverse stresses, such as extremely high and low temperatures, oxidative stress, and desiccation, which can result in protein homeostasis imbalance. Molecular chaperones function as key components that aid protein folding and prevent protein denaturation. Pseudomonas, an ecologically important bacterial genus, includes human and plant pathogens as well as growth-promoting symbionts and species useful for bioremediation. In this review, we focus on protein quality control systems, particularly molecular chaperones, in ecologically diverse species of Pseudomonas, including the opportunistic human pathogen Pseudomonas aeruginosa, the plant pathogen Pseudomonas syringae, the soil species Pseudomonas putida, and the psychrophilic Pseudomonas antarctica.

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Research Support, Non-U.S. Gov't

NOTE] Glyoxal Detoxification in Escherichia coli K-12 by NADPH Dependent Aldo-keto Reductases: Changhan Lee , Insook Kim , Chankyu Park; J. Microbiol. 2013;51(4):527-530. Published online August 30, 2013; DOI: https://doi.org/10.1007/s12275-013-3087-8

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Abstract PDF: Glyoxal (GO) and methylglyoxal (MG) are reactive carbonyl compounds that are accumulated in vivo through various pathways. They are presumably detoxified through multiple pathways including glutathione (GSH)-dependent/independent glyoxalase systems and NAD(P)H dependent reductases. Previously, we reported an involvement of aldo-ketoreductases (AKRs) in MG detoxification. Here, we investigated the role of various AKRs (YqhE, YafB, YghZ, YeaE, and YajO) in GO metabolism. Enzyme activities of the AKRs to GO were measured, and GO sensitivities of the corresponding mutants were compared. In addition, we examined inductions of the AKR genes by GO. The results indicate that AKRs efficiently detoxify GO, among which YafB, YghZ, and YeaE are major players.

Journal Article

NOTE] Mutations Upregulating the flhDC Operon of Escherichia coli K-12: Changhan Lee , Chankyu Park; J. Microbiol. 2013;51(1):140-144. Published online March 2, 2013; DOI: https://doi.org/10.1007/s12275-013-2212-z

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Abstract PDF

Bacterial motility is governed by the flhDC master operon that is under the control of factors like OmpR, LrhA, HdfR, and H-NS. Previously, derivatives of the wild-type MG1655 strain of E. coli K-12 with enhanced motility were found to contain insertion sequences (ISs) in the regulatory region of the flhDC operon. Here, we report that not only integrations of IS insertion sequences into the regulatory region of the flhDC operon, but also a missense mutation in the lrhA gene enhances motility by relieving transcriptional repression of the flhDC operon. Two novel IS insertions were found upstream of flhDC. So far, the relationships between the transacting factors and the cis-acting regulatory sequences associated with the flhDC operon have not been clearly established. In this study, it was found that effects of the cis- and trans-acting mutations were acting in parallel, suggesting their apparently independent regulation of flagellar expression.

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Research Support, Non-U.S. Gov'ts

Development of a Suicidal Vector-Cloning System Based on Butanal Susceptibility Due to an Expression of YqhD Aldehyde Reductase: Changhan Lee , Chankyu Park; J. Microbiol. 2012;50(2):249-255. Published online April 27, 2012; DOI: https://doi.org/10.1007/s12275-012-1438-5

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Abstract PDF: Previously, we observed butanal/propanal sensitivity of Escherichia coli K-12 when cells overexpress YqhD protein, a NADPH dependent aldehyde reductase, possibly due to an accumulation of butanol/propanol in vivo as the reaction products. Based on this finding, we developed a suicidal vector-cloning system derived from pUC19, in which lacZ was substituted with the yqhD gene. As a result, when foreign DNA was inserted into its multiple cloning sites by disrupting an expression of YqhD, the recombinants survived on butanal/propanal containing plate, whereas cells containing the YqhD vector died because of the alcohol production by YqhD. The cloning efficiency, estimated based on colony PCR and enzyme digestion, was achieved more than 90% when the suicidal vector system was used. Moreover, the plasmid vector itself was stably maintained in the cell, presumably due to its ability to remove toxic aldehydes being accumulated in E. coli cell by metabolic stress.

Screening of Genes Related to Methylglyoxal Susceptibility: Insook Kim , Joonho Kim , Bumchan Min , Changhan Lee , Chankyu Park; J. Microbiol. 2007;45(4):339-343.; DOI: https://doi.org/2563 [pii]

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Abstract PDF: Methylglyoxal (MG) is a reactive metabolite known to accumulate in certain physiological conditions. We attempted to isolate genes associated with this metabolite by genome-wide mutagenesis with TnphoA derivative. After screening on methylglyoxal-containing plate, we obtained insertions in three different genes, ydbD, yjjQ, and yqiI, which gave rise to reproducible MG-sensitive phenotypes in glyoxalase-deficient strain. In addition to its MG sensitivity, the insertion in yqiI exhibited an impaired motility resulting from a reduced flagellar expression.

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