Journal of Microbiology

Reviews

Adenoviral Vector System: A Comprehensive Overview of Constructions, Therapeutic Applications and Host Responses.: Anyeseu Park, Jeong Yoon Lee; J. Microbiol. 2024;62(7):491-509. Published online July 22, 2024; DOI: https://doi.org/10.1007/s12275-024-00159-4

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Abstract: Adenoviral vectors are crucial for gene therapy and vaccine development, offering a platform for gene delivery into host cells. Since the discovery of adenoviruses, first-generation vectors with limited capacity have evolved to third-generation vectors flacking viral coding sequences, balancing safety and gene-carrying capacity. The applications of adenoviral vectors for gene therapy and anti-viral treatments have expanded through the use of in vitro ligation and homologous recombination, along with gene editing advancements such as CRISPR-Cas9. Current research aims to maintain the efficacy and safety of adenoviral vectors by addressing challenges such as pre-existing immunity against adenoviral vectors and developing new adenoviral vectors from rare adenovirus types and non-human species. In summary, adenoviral vectors have great potential in gene therapy and vaccine development. Through continuous research and technological advancements, these vectors are expected to lead to the development of safer and more effective treatments.

The Microbiome Matters: Its Impact on Cancer Development and Therapeutic Responses: In‑Young Chung, Jihyun Kim, Ara Koh; J. Microbiol. 2024;62(3):137-152. Published online April 8, 2024; DOI: https://doi.org/10.1007/s12275-024-00110-7

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Abstract: In the evolving landscape of cancer research, the human microbiome emerges as a pivotal determinant reshaping our understanding of tumorigenesis and therapeutic responses. Advanced sequencing technologies have uncovered a vibrant microbial community not confned to the gut but thriving within tumor tissues. Comprising bacteria, viruses, and fungi, this diverse microbiota displays distinct signatures across various cancers, with most research primarily focusing on bacteria. The correlations between specifc microbial taxa within diferent cancer types underscore their pivotal roles in driving tumorigenesis and infuencing therapeutic responses, particularly in chemotherapy and immunotherapy. This review amalgamates recent discoveries, emphasizing the translocation of the oral microbiome to the gut as a potential marker for microbiome dysbiosis across diverse cancer types and delves into potential mechanisms contributing to cancer promotion. Furthermore, it highlights the adverse efects of the microbiome on cancer development while exploring its potential in fortifying strategies for cancer prevention and treatment.

Journal Articles

Syntaxin17 Restores Lysosomal Function and Inhibits Pyroptosis Caused by Acinetobacter baumannii.: Zhiyuan An, Wenyi Ding; J. Microbiol. 2024;62(4):315-325. Published online March 7, 2024; DOI: https://doi.org/10.1007/s12275-024-00109-0

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Abstract: Acinetobacter baumannii (A. baumannii) causes autophagy flux disorder by degrading STX17, resulting in a serious inflammatory response. It remains unclear whether STX17 can alter the inflammatory response process by controlling autolysosome function. This study aimed to explore the role of STX17 in the regulation of pyroptosis induced by A. baumannii. Our findings indicate that overexpression of STX17 enhances autophagosome degradation, increases LAMP1 expression, reduces Cathepsin B release, and improves lysosomal function. Conversely, knockdown of STX17 suppresses autophagosome degradation, reduces LAMP1 expression, augments Cathepsin B release, and accelerates lysosomal dysfunction. In instances of A. baumannii infection, overexpression of STX17 was found to improve lysosomal function and reduce the expression of mature of GSDMD and IL-1β, along with the release of LDH, thus inhibiting pyroptosis caused by A. baumannii. Conversely, knockdown of STX17 led to increased lysosomal dysfunction and further enhanced the expression of mature of GSDMD and IL-1β, and increased the release of LDH, exacerbating pyroptosis induced by A. baumannii. These findings suggest that STX17 regulates pyroptosis induced by A. baumannii by modulating lysosomal function.

Functional analysis of ascP in Aeromonas veronii TH0426 reveals a key role in the regulation of virulence: Yongchao Guan , Meng Zhang , Yingda Wang , Zhongzhuo Liu , Zelin Zhao , Hong Wang , Dingjie An , Aidong Qian , Yuanhuan Kang , Wuwen Sun , Xiaofeng Shan; J. Microbiol. 2022;60(12):1153-1161. Published online November 10, 2022; DOI: https://doi.org/10.1007/s12275-022-2373-8

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Abstract: Aeromonas veronii is a pathogen which can induce diseases in humans, animals and aquatic organisms, but its pathogenic mechanism and virulence factors are still elusive. In this study, we successfully constructed a mutant strain (ΔascP) by homologous recombination. The results showed that the deletion of the ascP gene significantly down-regulated the expression of associated effector proteins in A. veronii compared to its wild type. The adhesive and invasive abilities of ΔascP to EPC cells were 0.82-fold lower in contrast to the wild strain. The toxicity of ΔascP to cells was decreased by about 2.91-fold (1 h) and 1.74-fold (2 h). Furthermore, the LD50 of the mutant strain of crucian carp was reduced by 19.94-fold, and the virulence was considerably attenuated. In contrast to the wild strain, the ΔascP content in the liver and spleen was considerably lower. The titers of serum cytokines (IL-8, TNF-α, and IL-1β) in crucian carp after the infection of the ΔascP strain were considerably lower in contrast to the wild strain. Hence, the ascP gene is essential for the etiopathogenesis of A. veronii TH0426.

Review

[MINIREVIEW]Regulation of gene expression by protein lysine acetylation in Salmonella: Hyojeong Koo , Shinae Park , Min-Kyu Kwak , Jung-Shin Lee; J. Microbiol. 2020;58(12):979-987. Published online November 17, 2020; DOI: https://doi.org/10.1007/s12275-020-0483-8

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12 Citations

Abstract: Protein lysine acetylation influences many physiological functions, such as gene regulation, metabolism, and disease in eukaryotes. Although little is known about the role of lysine acetylation in bacteria, several reports have proposed its importance in various cellular processes. Here, we discussed the function of the protein lysine acetylation and the post-translational modifications (PTMs) of histone-like proteins in bacteria focusing on Salmonella pathogenicity. The protein lysine residue in Salmonella is acetylated by the Pat-mediated enzymatic pathway or by the acetyl phosphate-mediated non-enzymatic pathway. In Salmonella, the acetylation of lysine 102 and lysine 201 on PhoP inhibits its protein activity and DNAbinding, respectively. Lysine acetylation of the transcriptional regulator, HilD, also inhibits pathogenic gene expression. Moreover, it has been reported that the protein acetylation patterns significantly differ in the drug-resistant and -sensitive Salmonella strains. In addition, nucleoid-associated proteins such as histone-like nucleoid structuring protein (H-NS) are critical for the gene silencing in bacteria, and PTMs in H-NS also affect the gene expression. In this review, we suggest that protein lysine acetylation and the post-translational modifications of H-NS are important factors in understanding the regulation of gene expression responsible for pathogenicity in Salmonella.

Journal Article

Characterization of a novel dsRNA mycovirus of Trichoderma atroviride NFCF377 reveals a member of “Fusagraviridae” with changes in antifungal activity of the host fungus: Jeesun Chun , Byeonghak Na , Dae-Hyuk Kim; J. Microbiol. 2020;58(12):1046-1053. Published online October 23, 2020; DOI: https://doi.org/10.1007/s12275-020-0380-1

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9 Citations

Abstract: Trichoderma atroviride is a common fungus found in various ecosystems that shows mycoparasitic ability on other fungi. A novel dsRNA virus was isolated from T. atroviride NFCF377 strain and its molecular features were analyzed. The viral genome consists of a single segmented double-stranded RNA and is 9,584 bp in length, with two discontinuous open reading frames (ORF1 and ORF2). A mycoviral structural protein and an RNA-dependent RNA polymerase (RdRp) are encoded by ORF1 and ORF2, respectively, between which is found a canonical shifty heptameric signal motif (AAAAAAC) followed by an RNA pseudoknot. Analysis of sequence similarity and phylogeny showed that it is closely related to members of the proposed family “Fusagraviridae”, with a highest similarity to the Trichoderma atroviride mycovirus 1 (TaMV1). Although the sequence similarity of deduced amino acid to TaMV1 was evident, sequence deviations were distinctive at untranslated regions (UTRs) due to the extended size. Thus, we inferred this dsRNA to be a different strain of Trichoderma atroviride mycovirus 1 (TaMV1-NFCF377). Electron microscopy image exhibited an icosahedral viral particle of 40 nm diameter. Virus-cured isogenic isolates were generated and no differences in growth rate, colony morphology, or conidia production were observed between virus-infected and virus-cured strains. However, culture filtrates of TaMV1- NFCF377-infected strain showed enhanced antifungal activity against the plant pathogen Rhizoctonia solani but not to edible mushroom Pleurotus ostreatus. These results suggested that TaMV1-NFCF377 affected the metabolism of the fungal host to potentiate antifungal compounds against a plant pathogen, but this enhanced antifungal activity appeared to be species-specific.

Reviews

MINIREVIEW] Development of bacteria as diagnostics and therapeutics by genetic engineering: Daejin Lim , Miryoung Song; J. Microbiol. 2019;57(8):637-643. Published online May 11, 2019; DOI: https://doi.org/10.1007/s12275-019-9105-8

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18 Citations

Abstract: Bacteria sense and respond to the environment, communicate, and continuously interact with their surroundings, including host bodies. For more than a century, engineers have been trying to harness the natural ability of bacteria as live biotherapeutics for the treatment of diseases. Recent advances in synthetic biology facilitate the enlargement of the repertoire of genetic parts, tools, and devices that serve as a framework for biotherapy. This review describes bacterial species developed for specific diseases shown in in vitro studies and clinical stages. Here, we focus on drug delivery by programing bacteria and discuss the challenges for safety and improvement.

MINIREVIEW] Synthetic lethal interaction between oxidative stress response and DNA damage repair in the budding yeast and its application to targeted anticancer therapy: Ji Eun Choi , Woo-Hyun Chung; J. Microbiol. 2019;57(1):9-17. Published online December 29, 2018; DOI: https://doi.org/10.1007/s12275-019-8475-2

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6 Citations

Abstract: Synthetic lethality is an extreme form of negative genetic epistasis that arises when a combination of functional deficiency in two or more genes results in cell death, whereas none of the single genetic perturbations are lethal by themselves. This unconventional genetic interaction is a modification of the concept of essentiality that can be exploited for the purpose of targeted cancer therapy. The yeast Saccharomyces cerevisiae has been pivotally used for early large-scale synthetic lethal screens due to its experimental advantages, but recent advances in gene silencing technology have now made direct high-throughput analysis possible in higher organisms. Identification of tumor-specific alterations and characterization of the mechanistic principles underlying synthetic lethal interaction are the key to applying synthetic lethality to clinical cancer treatment by enabling genome-driven oncological research. Here, we provide emerging ideas on the synthetic lethal interactions in budding yeast, particularly between cellular processes responsible for oxidative stress response and DNA damage repair, and discuss how they can be appropriately utilized for context-dependent cancer therapeutics.

Journal Articles

Photodynamic antimicrobial activity of new porphyrin derivatives against methicillin resistant Staphylococcus aureus: Hüseyin Ta&# , Ay&# , Nermin Topalo&# , Vildan Alptüzün; J. Microbiol. 2018;56(11):828-837. Published online October 24, 2018; DOI: https://doi.org/10.1007/s12275-018-8244-7

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26 Citations

Abstract: Methicillin resistant Staphylococcus aureus (MRSA) with multiple drug resistance patterns is frequently isolated from skin and soft tissue infections that are involved in chronic wounds. Today, difficulties in the treatment of MRSA associated infections have led to the development of alternative approaches such as antimicrobial photodynamic therapy. This study aimed to investigate photoinactivation with cationic porphyrin derivative compounds against MRSA in in-vitro conditions. In the study, MRSA clinical isolates with different antibiotic resistance profiles were used. The newly synthesized cationic porphyrin derivatives (PM, PE, PPN, and PPL) were used as photosensitizer, and 655 nm diode laser was used as light source. Photoinactivation experiments were performed by optimizing energy doses and photosensitizer concentrations. In photoinactivation experiments with different energy densities and photosensitizer concentrations, more than 99% reduction was achieved in bacterial cell viability. No decrease in bacterial survival was observed in control groups. It was determined that there was an increase in photoinactivation efficiency by increasing the energy dose. At the energy dose of 150 J/cm2 a survival reduction of over 6.33 log10 was observed in each photosensitizer type. While 200 μM PM concentration was required for this photoinactivation, 12.50 μM was sufficient for PE, PPN, and PPL. In our study, antimicrobial photodynamic therapy performed with cationic porphyrin derivatives was found to have potent antimicrobial efficacy against multidrug resistant S. aureus which is frequently isolated from wound infections.

Anti protein A antibody-gold nanorods conjugate: a targeting agent for selective killing of methicillin resistant Staphylococcus aureus using photothermal therapy method: Rasoul Shokri , Mojtaba Salouti , Rahim Sorouri Zanjani; J. Microbiol. 2015;53(2):116-121. Published online January 28, 2015; DOI: https://doi.org/10.1007/s12275-015-4519-4

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24 Citations

Abstract: The high prevalence of methicillin resistant Staphylococcus aureus (MRSA) and developing resistance to antibiotics requires new approaches for treatment of infectious diseases due to this bacterium. In this study, we developed a targeting agent for selective killing of MRSA using photothermal therapy method based on anti protein A antibody and gold nanorods (GNRs). Polystyrene sulfonate (PSS) coated GNRs were conjugated with anti protein A antibody. The FT-IR and UV-vis analyses approved the formation of anti protein A antibody-gold nanorods conjugate. In vitro study of photothermal therapy showed 82% reduction in the MRSA cells viability which was significantly greater than the ablation effect of free GNRs and laser alone. Significant accumulation of anti protein A antibody-GNRs in the infected muscle in comparison with normal muscle approved the targeting ability of new agent. In vivo study of photothermal therapy resulted in a significant reduction (73%) in the bacterial cells viability in the infected mouse model. These results demonstrated the ability of anti protein A antibody-GNRs conjugate in combination with NIR laser energy for selective killing of MRSA in mouse model.

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

Neutralization Potential of the Plasma of HIV-1 Infected Indian Patients in the Context of Anti-V3 Antibody Content and Antiretroviral Theraphy: Alok Kumar Choudhary , Raiees Andrabi , Somi Sankaran Prakash , Rajesh Kumar , Shubhasree Dutta Choudhury Choudhury , Naveet Wig , Ashutosh Biswas , Anjali Hazarika , Kalpana Luthra; J. Microbiol. 2012;50(1):149-154. Published online February 27, 2012; DOI: https://doi.org/10.1007/s12275-012-1246-y

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8 Citations

Abstract: We assessed the anti-V3 antibody content and viral neutralization potential of the plasma of 63 HIV-1-infected patients (antiretroviral naïve=39, treated=24) against four primary isolates (PIs) of clade C and a tier 1 clade B isolate SF162. Depletion and inhibition of anti-V3 antibodies in the plasma of five patients with high titers of anti-V3 antibodies led to modest change in the neutralization percentage against two PIs (range 0–21%). The plasma of antiretroviral-treated patients exhibited higher neutralization potential than that of the drug-naïve plasmas against the four PIs tested which was further evidenced by a follow-up study.

Antibacterial Efficacy of Lytic Pseudomonas Bacteriophage in Normal and Neutropenic Mice Models: Birendra R. Tiwari , Shukho Kim , Marzia Rahman , Jungmin Kim; J. Microbiol. 2011;49(6):994-999. Published online December 28, 2011; DOI: https://doi.org/10.1007/s12275-011-1512-4

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61 Citations

Abstract: Recently, lytic bacteriophages (phages) have been focused on treating bacterial infectious diseases. We investigated the protective efficacy of a novel Pseudomonas aeruginosa phage, PA1Ø, in normal and neutropenic mice. A lethal dose of P. aeruginosa PAO1 was administered via the intraperitoneal route and a single dose of PA1Ø with different multiplicities of infection (MOI) was treated into infected mice. Immunocompetent mice infected with P. aeruginosa PAO1 were successfully protected by PA1Ø of 1 MOI, 10 MOI or 100 MOI with 80% to 100% survival rate. No viable bacteria were found in organ samples after 48 h of the phage treatment. Phage clearing patterns were different in the presence or absence of host bacteria but PA1Ø disappeared from all organs after 72 h except spleen in the presence of host bacteria. On the contrary, PA1Ø treatment could not protect neutropenic mice infected with P. aeruginosa PAO1 even though could extend their lives for a short time. In in vitro phage-neutrophil bactericidal test, a stronger bactericidal effect was observed in phage-neutrophil co-treatment than in phage single treatment without neutrophils, suggesting phage-neutrophil co-work is essential for the efficient killing of bacteria in the mouse model. In conclusion, PA1Ø can be possibly utilized in future phage therapy endeavors since it exhibited strong protective effects against virulent P. aeruginosa infection.

The Photodynamic Effect of Methylene Blue and Toluidine Blue on Candida albicans Is Dependent on Medium Conditions: Gabriela Guimarães Carvalho , Monalisa Poliana Felipe , Maricilia Silva Costa; J. Microbiol. 2009;47(5):619-623. Published online October 24, 2009; DOI: https://doi.org/10.1007/s12275-009-0059-0

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48 Citations

Abstract: Due to the increased number of immunocompromised patients, the infections associated with the pathogen of the genus Candida and other fungi have increased dramatically. Photodynamic antimicrobial chemotherapy (PACT) has been presented as a potential antimicrobial therapy, in a process that combines light and a photosensitizing drug, which promotes a phototoxic response by the treated cells. In this work, we studied the effects of the different medium conditions during PACT, using either methylene blue (MB) or toluidine blue (TB) on Candida albicans. The inhibition of the growth produced by PACT was decreased for different pH values (6.0, 7.0, and 8.0) in a buffered medium. The phototoxic effects were observed only in the presence of saline (not buffered medium). PACT was modulated by calcium in a different manner using either MB or TB. Also when using MB both verapamil or sodium azide were able to decrease the phototoxic effects on the C. albicans. These results show that PACT is presented as a new and promising antifungal therapy, however, new studies are necessary to understand the mechanism by which this event occurs.

Review

Strategies Against Human Papillomavirus Infection and Cervical Cancer: Woon-Won Jung , Taehoon Chun , Donggeun Sul , Kwang Woo Hwang , Hyung-Sik Kang , Duck Joo Lee , In-Kwon Han; J. Microbiol. 2004;42(4):255-266.; DOI: https://doi.org/2112 [pii]

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Abstract: Papillomaviruses infect a wide variety of animals, including humans. The human papillomavirus (HPV), in particular, is one of the most common causes of sexually transmitted disease. More than 200 types of HPV have been identified by DNA sequence data, and 85 HPV genotypes have been well characterized to date. HPV can infect the basal epithelial cells of the skin or inner tissue linings, and are, accordingly, categorized as either cutaneous or mucosal type. HPV is associated with a panoply of clinical conditions, ranging from innocuous lesions to cervical cancer. In the early 1980s, studies first reported a link between cervical cancer and genital HPV infection. Genital HPV infections are now recognized to be a major risk factor in at least 95% of cervical cancers. 30 different HPV genotypes have been identified as causative of sexually transmitted diseases, most of which induce lesions in the cervix, vagina, vulva, penis, and anus, as the result of sexual contact. There is also direct evidence demonstrating that at least four of these genotypes are prerequisite factors in cervical cancer. The main aim of this review was to evaluate the current literature regarding the pathovirology, diagnostics, vaccines, therapy, risk groups, and further therapeutic directions for HPV infections. In addition, we reviewed the current status of HPV infections in South Korean women, as evidenced by our data.

Journal Article

Comparative Analysis of Intracellular Trans-Splicing Ribozyme Activity Against Hepatitis C Virus Internal Ribosome Entry Site: Kyung-Ju Ryu Seong-Wook Lee; J. Microbiol. 2004;42(4):361-364.; DOI: https://doi.org/2097 [pii]

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Abstract: Internal ribosome entry site (IRES) of the hepatitis C virus (HCV) is known to be essential for HCV replication and most conserved among HCV variants. Hence, IRES RNA is a good therapeutic target for RNA-based inhibitors, such as ribozymes. We previously proposed a new anti-HCV modulation strategy based on trans-splicing ribozymes, which can selectively replace HCV transcripts with a new RNA that exerts anti-HCV activity. To explore this procedure, sites which are accessible to ribozymes in HCV IRES were previously determined by employing an RNA mapping method in vitro. In this study, we evaluate the intracellular accessibility of the ribozymes by comparing the trans-splicing activities in cells of several ribozymes targeting different sites of the HCV IRES RNA. We assessed the intracellular activities of the ribozymes by monitoring their target-specific induction degree of both reporter gene activity and cytotoxin expression. The ribozyme capable of targeting the most accessible site identified by the mapping studies then harbored the most active trans-splicing activity in cells. These results suggest that the target sites predicted to be accessible are truly the most accessible in the cells, and thus, could be applied to the development of various RNA-based anti-HCV therapies.

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