Journal of Microbiology

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Pycnogenol reduces the expression of P. aeruginosa T3SS and inflammatory response in NCI-H292 cells: Seung-Ho Kim, Da Yun Seo, Sang-Bae Han, Un-Hwan Ha, Ji-Won Park, Kyung-Seop Ahn; J. Microbiol. 2025;63(10):2503004. Published online September 19, 2025; DOI: https://doi.org/10.71150/jm.2503004

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Abstract PDF Supplementary Material: Nosocomial infections caused by Pseudomonas aeruginosa (P. aeruginosa) have become increasingly common, particularly among immunocompromised individuals, who experience high mortality rates and prolonged treatment durations due to the limited availability of effective therapies. In this study, we screened for anti-ExoS compounds targeting P. aeruginosa and identified pycnogenol (PYC) as a potent inhibitor of the type III secretion system (T3SS), a major virulence mechanism responsible for the translocation of effectors such as ExoS. Using ELISA, western blotting, and real-time PCR analyses in both P. aeruginosa and infected H292 cells, we found that PYC significantly reduced T3SS activity. Mechanistically, PYC suppressed the transcription of T3SS-related genes by downregulating exsA expression in P. aeruginosa. Furthermore, pretreatment with PYC attenuated the cytotoxic effects and reduced the expression of proinflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-18 (IL-18), in P. aeruginosa-infected H292 cells. These effects were associated with the inhibition of NF-κB signaling and inflammasome activation. Taken together, our findings suggest that PYC may serve as a promising therapeutic candidate against P. aeruginosa infections by targeting T3SS-mediated virulence and modulating host inflammatory responses.

Journal Articles

Weigela florida inhibits the expression of inflammatory mediators induced by Pseudomonas aeruginosa and Staphylococcus aureus infection: Hyo Bin Kim , Soomin Cho , Yeji Lee , Weihui Wu , Un-Hwan Ha; J. Microbiol. 2022;60(6):649-656. Published online April 30, 2022; DOI: https://doi.org/10.1007/s12275-022-1638-6

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Inflammatory responses involve the action of inflammatory mediators that are necessary for the clearance of invading bacterial pathogens. However, excessive production of inflammatory mediators can damage tissues, thereby impairing bacterial clearance. Here, we examined the effects of Weigela florida on the expression of inflammatory cytokines induced by Pseudomonas aeruginosa or Staphylococcus aureus infection in macrophages. The results showed that pre-treatment with W. florida markedly downregulated the bacterial infectionmediated expression of cytokines. Additionally, post-treatment also triggered anti-inflammatory effects in cells infected with S. aureus to a greater extent than in those infected with P. aeruginosa. Bacterial infection activated inflammation-associated AKT (Thr308 and Ser473)/NF-κB and MAPK (p38, JNK, and ERK) signaling pathways, whereas W. florida treatment typically inhibited the phosphorylation of AKT/NF‐κB and p38/JNK, supporting the anti‐inflammatory effects of W. florida. The present results suggest that W. florida decreases the infection-mediated expression of inflammatory mediators by inhibiting the AKT/NF-κB and MAPK signaling pathways, implying that it may have potential use as an inhibitory agent of excessive inflammatory responses.

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Identification of D-amino acid dehydrogenase as an upstream regulator of the autoinduction of a putative acyltransferase in Corynebacterium glutamicum: Jung-Hoon Lee , Yong-Jae Kim , Hee-Sung Shin , Heung-Shick Lee , Shouguang Jin , Un-Hwan Ha; J. Microbiol. 2016;54(6):432-439. Published online May 27, 2016; DOI: https://doi.org/10.1007/s12275-016-6046-3

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Abstract PDF

Expression of a putative acyltransferase encoded by NCgl- 0350 of Corynebacterium glutamicum is induced by cell-free culture fluids obtained from stationary-phase growth of both C. glutamicum and Pseudomonas aeruginosa, providing evidence for interspecies communication. Here, we further confirmed that such communication occurs by showing that acyltransferase expression is induced by culture fluid obtained from diverse Gram-negative and -positive bacterial strains, including Escherichia coli, Salmonella Typhimurium, Bacillus subtilis, Staphylococcus aureus, Mycobacterium sp. strain JC1, and Mycobacterium smegmatis. A homologous acyltransferase encoded by PA5238 of P. aeruginosa was also induced by fluids obtained from P. aeruginosa as well as other bacterial strains, as observed for NCgl0350 of C. glutamicum. Because C. glutamicum is difficult to study using molecular approaches, the homologous gene PA5238 of P. aeruginosa was used to identify PA5309 as an upstream regulator of expression. A homologous D-amino acid dehydrogenase encoded by NCgl- 2909 of C. glutamicum was cloned based on amino acid similarity to PA5309, and its role in the regulation of NCgl0350 expression was confirmed. Moreover, NCgl2909 played positive roles in growth of C. glutamicum. Thus, we identified a D-amino acid dehydrogenase as an upstream regulator of the autoinduction of a putative acyltransferase in C. glutamicum.

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Enhanced Bacterial Growth and Gene Expression of D-Amino Acid Dehydrogenase With D-Glutamate as the Sole Carbon Source
Takeshi Naganuma, Yoshiakira Iinuma, Hitomi Nishiwaki, Ryota Murase, Kazuo Masaki, Ryosuke Nakai
Frontiers in Microbiology.2018;[Epub] CrossRef

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TatC-dependent translocation of pyoverdine is responsible for the microbial growth suppression: Yeji Lee , Yong-Jae Kim , Jung-Hoon Lee , Hyung Eun Yu , Kiho Lee , Shouguang Jin , Un-Hwan Ha; J. Microbiol. 2016;54(2):122-130. Published online February 2, 2016; DOI: https://doi.org/10.1007/s12275-016-5542-9

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Infections are often not caused by a colonization of Pseudomonas aeruginosa alone but by a consortium of other bacteria. Little is known about the impact of P. aeruginosa on the growth of other bacteria upon coinfection. Here, cellree culture supernatants obtained from P. aeruginosa suppressed the growth of a number of bacterial strains such as Corynebacterium glutamicum, Bacillus subtilis, Staphylococcus aureus, and Agrobacterium tumefaciens, but had little effect on the growth of Escherichia coli and Salmonella Typhimurium. The growth suppression effect was obvious when P. aeruginosa was cultivated in M9 minimal media, and the suppression was not due to pyocyanin, a well-known antimicrobial toxin secreted by P. aeruginosa. By performing transposon mutagenesis, PA5070 encoding TatC was identified, and the culture supernatant of its mutant did not suppress the growth. HPLC analysis of supernatants showed that pyoverdine was a secondary metabolite present in culture supernatants of the wild-type strain, but not in those of the PA5070 mutant. Supplementation of FeCl2 as a source of iron compromised the growth suppression effect of supernatants and also recovered biofilm formation of S. aureus, indicating that pyoverdine-mediated iron acquisition is responsible for the growth suppression. Thus, this study provides the action of TatC-dependent pyoverdine translocation for the growth suppression of other bacteria, and it might aid understanding of the impact of P. aeruginosa in the complex community of bacterial species upon coinfection.

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Characterization of the antagonistic potential of the glyphosate-tolerant Pseudomonas resinovorans SZMC 25872 strain against the plant pathogenic bacterium Agrobacterium tumefaciens
Anuar R. Zhumakayev, Mónika Varga, Mónika Vörös, Sándor Kocsubé, Pramod W. Ramteke, András Szekeres, Csaba Vágvölgyi, Lóránt Hatvani, Tamás Marik
Frontiers in Plant Science.2022;[Epub] CrossRef
Ecology drives the evolution of diverse social strategies in Pseudomonas aeruginosa
Alexandre R. T. Figueiredo, Andreas Wagner, Rolf Kümmerli
Molecular Ecology.2021; 30(20): 5214. CrossRef
Mycobacterium abscessus subsp. abscessus Is Capable of Degrading Pseudomonas aeruginosa Quinolone Signals
Franziska S. Birmes, Timo Wolf, Thomas A. Kohl, Kai Rüger, Franz Bange, Jörn Kalinowski, Susanne Fetzner
Frontiers in Microbiology.2017;[Epub] CrossRef

Pseudomonas aeruginosa-induced IL-1β Production is Inhibited by Sophora flavescens via the NF-κB/inflammasome Pathways: Jung-Hoon Lee , Heesung Shin , Yong-Jae Kim , Se-Hwan Paek , Shouguang Jin , Un-Hwan Ha; J. Microbiol. 2014;52(12):1044-1049. Published online November 29, 2014; DOI: https://doi.org/10.1007/s12275-014-4512-3

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Abstract PDF

The proinflammatory cytokine interleukin-1β plays an important role in protecting the host against airway infection; however, it can also trigger a massive influx of neutrophils into the airways, causing tissue damage. Anti-inflammatory treatments are particularly in demand for patients suffering from chronic inflammatory diseases. Sophora flavescens is a traditional herbal medicine used to reduce inflammation, but no study has examined its ability to block IL-1β production. Here, we show that S. flavescens reduced the Pseudomonas aeruginosa-induced expression of IL-1β by lung epithelial cells and macrophages. S. flavescens was also effective at reducing IL-1β production induced by either Staphylococcus aureus or phorbol 12-myristate 13-acetate, indicating that the effect is generalizable to diverse inflammatory stimuli. In addition, S. flavescens blocked the phosphorylation of IKKα/β, key upstream kinases involved in the degradation of IκBα, and the cleavage of caspase-1, a key component of the inflammasome. Thus, this study demonstrates that S. flavescens exerts its anti-inflammatory effects by blocking P. aeruginosa-mediated NF-κB/inflammasome activation and the subsequent production of IL-1β.

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Effects of Sophora flavescens ethanol extract supplementation in high soybean meal diets on growth, intestinal antioxidant status and immune response in Pearl Gentian grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂)
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Pneumolysin-Mediated Expression of β-Defensin 2 Is Coordinated by p38 MAP Kinase-MKP1 in Human Airway Cells: Yong-Jae Kim , Hee-Sung Shin , Jung-Hoon Lee , Yong Woo Jung , Hyong-Bai Kim , Un-Hwan Ha; J. Microbiol. 2013;51(2):194-199. Published online April 27, 2013; DOI: https://doi.org/10.1007/s12275-013-2579-x

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Abstract PDF

Antimicrobial peptides act as important innate immune defense mediators against invading microbes such as Streptococcus pneumoniae. Among a number of antimicrobial peptides, β-defensin 2 (BD2) has strong antimicrobial activity against S. pneumoniae. However, little is known about the molecular signaling mechanisms leading to the BD2 expression. Here, we report that BD2 is strongly induced by S. pneumoniae in human airway cells including human middle-ear cells. Among diverse pneumococcal virulence factors, pneumolysin is required for inducing BD2 whose expression is under the control of p38 mitogen-activated protein kinase (MAPK). Pneumolysin also selectively regulates the expression of MAPK phosphatase 1 (MKP1), which inhibits the p38 signaling pathway, thereby leading to upregulation of BD2 to mount an effective defense against S. pneumoniae infection. These results provide novel insights into the molecular mechanisms underlying the coordinative regulation of BD2 expression via p38-MKP1 in the pathogenesis of airway infectious diseases.

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