• Title/Summary/Keyword: Microbial drug resistance

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Recent Advances of Therapeutic Targets for the Treatment of Periodontal Disease

  • Kim, Woo Jin;Soh, Yunjo;Heo, Seok-Mo
    • Biomolecules & Therapeutics
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    • v.29 no.3
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    • pp.263-267
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    • 2021
  • Periodontal disease is primarily associated with bacterial infection such as dental plaque. Dental plaque, an oral biofilm harboring a complex microbial community, can cause various inflammatory reactions in periodontal tissue. In many cases, the local bacterial invasion and host-mediated immune responses lead to severe alveolar bone destruction. To date, plaque control, non-surgical, and surgical interventions have been the conventional periodontal treatment modalities. Although adjuvant therapies including antibiotics or supplements have accompanied these procedures, their usage has been limited by antibiotic resistance, as well as their partial effectiveness. Therefore, new strategies are needed to control local inflammation in the periodontium and host immune responses. In recent years, target molecules that modulate microbial signaling mechanisms, host inflammatory substances, and bone immune responses have received considerable attention by researchers. In this review, we introduce three approaches that suggest a way forward for the development of new treatments for periodontal disease; (1) quorum quenching using quorum sensing inhibitors, (2) inflammasome targeting, and (3) use of FDA-approved anabolic agents, including Teriparatide and sclerostin antibody.

Disruption of Established Bacterial and Fungal Biofilms by a Blend of Enzymes and Botanical Extracts

  • Gitte S. Jensen;Dina Cruickshank;Debby E. Hamilton
    • Journal of Microbiology and Biotechnology
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    • v.33 no.6
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    • pp.715-723
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    • 2023
  • Microbial biofilms are resilient, immune-evasive, often antibiotic-resistant health challenges, and increasingly the target for research into novel therapeutic strategies. We evaluated the effects of a nutraceutical enzyme and botanical blend (NEBB) on established biofilm. Five microbial strains with known implications in chronic human illnesses were tested: Candida albicans, Staphylococcus aureus, Staphylococcus simulans (coagulase-negative, penicillin-resistant), Borrelia burgdorferi, and Pseudomonas aeruginosa. The strains were allowed to form biofilm in vitro. Biofilm cultures were treated with NEBB containing enzymes targeted at lipids, proteins, and sugars, also containing the mucolytic compound N-acetyl cysteine, along with antimicrobial extracts from cranberry, berberine, rosemary, and peppermint. The post-treatment biofilm mass was evaluated by crystal-violet staining, and metabolic activity was measured using the MTT assay. Average biofilm mass and metabolic activity for NEBB-treated biofilms were compared to the average of untreated control cultures. Treatment of established biofilm with NEBB resulted in biofilm-disruption, involving significant reductions in biofilm mass and metabolic activity for Candida and both Staphylococcus species. For B. burgdorferi, we observed reduced biofilm mass, but the remaining residual biofilm showed a mild increase in metabolic activity, suggesting a shift from metabolically quiescent, treatment-resistant persister forms of B. burgdorferi to a more active form, potentially more recognizable by the host immune system. For P. aeruginosa, low doses of NEBB significantly reduced biofilm mass and metabolic activity while higher doses of NEBB increased biofilm mass and metabolic activity. The results suggest that targeted nutraceutical support may help disrupt biofilm communities, offering new facets for integrative combinational treatment strategies.

Evaluation of Ciclopirox as a Virulence-modifying Agent Against Multidrug Resistant Pseudomonas aeruginosa Clinical Isolates from Egypt

  • Zakaria, Azza S.;Edward, Eva A.;Mohamed, Nelly M.
    • Microbiology and Biotechnology Letters
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    • v.47 no.4
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    • pp.651-661
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    • 2019
  • Targeting the pathogen viability using drugs is associated with development of drug resistance due to selective pressure. Hence, there is an increased interest in developing agents that target bacterial virulence. In this study, the inhibitory effect of ciclopirox, an antifungal agent with iron chelation potential, on the microbial virulence factors was evaluated in 26 clinical MDR Pseudomonas aeruginosa isolates collected from Alexandria Main University Hospital, a tertiary hospital in Egypt. Treatment with 9 ㎍/ml ciclopirox inhibited the hemolytic activity in 70% isolates, reduced pyocyanin production, decreased protease secretion in 46% isolates, lowered twitching and swarming motility, and decreased biofilm formation by 1.5- to 4.5-fold. The quantitative real-time PCR analysis revealed that treatment with ciclopirox downregulated the expression levels of alkaline protease (aprA) and pyocyanin (phzA1). Ciclopirox is used to treat hematological malignancies and the systemic administration of ciclopirox is reported to have adequate oral absorption with a satisfactory drug safety profile. It is important to calculate the appropriate clinical dose and therapeutic index to reposition ciclopirox from a topical antifungal agent to a promising virulence-modifying agent agent against P. aeruginosa, a problematic Gram-negative pathogen.

Optimal First-line Eradication Regimens for Helicobacter pylori Infection in Patients with Clarithromycin Resistance: A Pilot Study (국내 클래리스로마이신 내성균에서 가장 효과적인 헬리코박터 제균 치료법)

  • Seo, Min Woo;Jeong, Yeon Jeong;Kim, Joon Sung;Kim, Byung Wook
    • The Korean journal of helicobacter and upper gastrointestinal research
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    • v.18 no.4
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    • pp.242-246
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    • 2018
  • Background/Aims: Helicobacter pylori eradication rates using first-line treatment have decreased due to clarithromycin resistance. The aim of this study was to investigate optimal eradication regimens for patients with clarithromycin resistance in Korea. Materials and Methods: A total of 72 patients with confirmed clarithromycin resistance were enrolled from August 2015 to July 2017. Patients were randomized to a 7-day bismuth quadruple therapy (BQT) regimen or a 7-day metronidazole triple therapy (MTT) regimen. Eradication was confirmed using the $^{13}C$-urea breath test. Results: There were no differences in baseline characteristics between the groups. Intention-to-treat eradication rates were 77.8% for the BQT group and 66.7% for the MTT group (P=0.293). Per protocol eradication rates were 87.5% for the BQT group and 77.4% for the MTT group (P=0.292). Adverse events were more frequent in the BQT group. Conclusions: Eradication rates using MTT were comparable to those using BQT, and adverse events were less frequent in the MTT group. Thus, MTT may be considered as a first-line regimen for patients with clarithromycin resistance. Since this was a pilot study, a study with a large group is required.

Host-Pathogen Interactions Operative during Mycobacteroides abscessus Infection

  • Eun-Jin Park;Prashanta Silwal;Eun-Kyeong Jo
    • IMMUNE NETWORK
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    • v.21 no.6
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    • pp.40.1-40.20
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    • 2021
  • Mycobacteroides abscessus (previously Mycobacterium abscessus; Mabc), one of rapidly growing nontuberculous mycobacteria (NTM), is an important pathogen of NTM pulmonary diseases (NTM-PDs) in both immunocompetent and immunocompromised individuals. Mabc infection is chronic and often challenging to treat due to drug resistance, motivating the development of new therapeutics. Despite this, there is a lack of understanding of the relationship between Mabc and the immune system. This review highlights recent progress in the molecular architecture of Mabc and host interactions. We discuss several microbial components that take advantage of host immune defenses, host defense pathways that can overcome Mabc pathogenesis, and how host-pathogen interactions determine the outcomes of Mabc infection. Understanding the molecular mechanisms underlying host-pathogen interactions during Mabc infection will enable the identification of biomarkers and/or drugs to control immune pathogenesis and protect against NTM infection.

Increased Sensitivity to Chloramphenicol by Inactivation of manB in Streptomyces coelicolor

  • Rajesh, Thangamani;Song, Eunjung;Lee, Bo-Rahm;Park, Sung-Hee;Jeon, Jong-Min;Kim, Eunjung;Sung, Changmin;Lee, Jae-Hun;Yoo, Dongwon;Park, Hyung-Yeon;Kim, Yun-Gon;Kim, Byung-Gee;Yang, Yung-Hun
    • Journal of Microbiology and Biotechnology
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    • v.22 no.10
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    • pp.1324-1329
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    • 2012
  • Phosphomannomutase (ManB) is involved in the biosynthesis of GDP-mannose, which is vital for numerous processes such as synthesis of carbohydrates, production of alginates and ascorbic acid, and post-translational modification of proteins. Here, we discovered that a deletion mutant of manB (BG101) in Streptomyces coelicolor (S. coelicolor) showed higher sensitivity to bacteriostatic chloramphenicol (CM) than the wild-type strain (M145), along with decreased production of CM metabolites. Deletion of manB also decreased the mRNA expression level of drug efflux pumps (i.e., cmlR1 and cmlR2) in S. coelicolor, resulting in increased sensitivity to CM. This is the first report on changes in antibiotic sensitivity to CM by deletion of one glycolysis-related enzyme in S. coelicolor, and the results suggest different approaches for studying the antibiotic-resistant mechanism and its regulation.

Mutations in Streptomycin Resistance Genes and Their Relationship to Streptomycin Resistance and Lineage of Mycobacterium tuberculosis Thai Isolates

  • Hlaing, Yin Moe;Tongtawe, Pongsri;Tapchaisri, Pramuan;Thanongsaksrikul, Jeeraphong;Thawornwan, Unchana;Archanachan, Buppa;Srimanote, Potjanee
    • Tuberculosis and Respiratory Diseases
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    • v.80 no.2
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    • pp.159-168
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    • 2017
  • Background: Streptomycin (SM) is recommended by the World Health Organization (WHO) as a part of standard regimens for retreating multidrug-resistant tuberculosis (MDR-TB) cases. The incidence of MDR-TB in retreatment cases was 19% in Thailand. To date, information on SM resistance (SMR) gene mutations correlated to the SMR of Mycobacterium tuberculosis Thai isolates is limited. In this study, the mutations in rpsL, rrs, gidB, and whiB7 were investigated and their association to SMR and the lineage of M. tuberculosis were explored. Methods: The lineages of 287 M. tuberculosis collected from 2007 to 2011 were identified by spoligotyping. Drug susceptibility profiles were evaluated by the absolute concentration method. Mutations in SMR genes of 46 SM-resistant and 55 SM-susceptible isolates were examined by DNA sequencing. Results: Three rpsL (Lys43Arg, Lys88Arg, and Lys88Thr) and two gidB (Trp45Ter and Gly69Asp) mutations were present exclusively in the SM resistant M. tuberculosis. Lys43Arg rpsL was the most predominant SMR mutations (69.6%) and prevailed among Beijing isolates (p<0.001). No SMR-related mutation in was found rrs. The combination of rpsL and gidB mutations provided 76.1% sensitivity for detecting SMR in M. tuberculosis Thai isolates. whiB7 was not responsible for SMR in SM resistant isolates lacking rpsL and rrs mutations. The significance of the three gidB mutations, 276A>C, 615A>G, and 330G>T, as lineage signatures for Beijing and EAI were underscored. This study identified 423G>A gidB as a novel sub-lineage marker for EAI6-BGD1. Conclusion: Our study suggested that the majority of SMR in M. tuberculosis Thai isolates were responsible by rpsL and gidB polymorphisms constantly providing the novel lineage specific makers.

The distribution and antimicrobial susceptibility of pathogenic microorganisms isolated from chicken slaughtering and processing procedure (닭 도계 및 가공공정 중 유해미생물의 분포와 항생제 감수성)

  • Seol, Kuk-Hwan;Kim, Ki Hyun;Jo, Su-Mi;Kim, Young Hwa;Kim, Hyun-Wook;Ham, Jun-Sang
    • Korean Journal of Agricultural Science
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    • v.42 no.1
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    • pp.29-35
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    • 2015
  • This study was performed to analyze the distribution and antimicrobial resistance of pathogenic microorganisms isolated from the carcass and environments of chicken processing plant located in Gyeonggi province from October to November in 2010. Chicken slaughterhouse was visited 3 times and totally 40 samples were collected from chicken carcass before and after washing (n=14), chicken cuts (n=7), cooling water (n=8), brine (n=2), cutting knives (n=7) and working plate (n=2). Whole-chicken rinsing technique (for chicken carcasses) and swab technique (for working plate and knives) were used to analyze the distribution of pathogenic microorganisms. In addition, brine and chilling water from storage tanks were gathered using sterilized tubes and used as samples. The matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) for whole cell fingerprinting in combination with a dedicated bioinformatic software tool was used to identify the isolated microorganisms. The pathogenic microorganisms, such as Bacillus cereus (n=8) and Staphylococcus aureus (n=9), were isolated form the chicken processing process (chicken carcasses of before and after chilling, chicken cuts, and working plate). The antimicrobial susceptibility of those isolated microorganisms was analyzed using 21 antimicrobial agents. In the case of B. cereus, it showed 100% of resistance to subclasses of penicillins and peptides, and it also resistant to cephalothin, a member of critically important antimicrobials (CIA), however there was no resistance (100% susceptible) to vancomycin and chloramphenicol. S. aureus showed 100% resistance to subclasses of peptides and some of penicillins (penicillin and oxacillin), however, it showed 100% susceptibility to cephalosporins (cefazolin and cephalothin). All of the tested pathogens showed multi drug resistance (MDR) more than 4 subclasses and one of B. cereus and S. aureus showed resistance to 9 subclasses. After the ban on using the antimicrobials in animal feed in July 2011, there would be some change in microbial distribution and antimicrobial resistance, and it still has a need to be analyzed.

Microbial isolates and antibiotic sensitivity in patients hospitalized with odontogenic infections at a tertiary center over 10 years

  • Gyu-Beom Kwon;Chul-Hwan Kim
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.49 no.4
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    • pp.198-207
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    • 2023
  • Objectives: This study investigated causative strains and their antibiotic sensitivity in patients who were hospitalized for maxillofacial odontogenic infections at a tertiary center in South Korea over the past 10 years with the aim of providing guidelines for the selection of appropriate empirical antibiotics. Materials and Methods: Patients with head and neck fascial space abscesses due to odontogenic infections who underwent incision and drainage surgery with pus culture tests between 2013 and 2022 at the Department of Oral and Maxillofacial Surgery, Dankook University Hospital were included. The bacterial isolates and antibiotic sensitivity of each strain were analyzed for 2013-2022, 2013-2017, and 2018-2022. The affected fascial spaces were classified into primary, secondary, and deep neck spaces. Results: In the 192 patients included in this study, 302 strains were detected. Viridans streptococcus had the highest frequency (51.7%), followed by Prevotella spp. (16.9%), Staphylococcus spp. (5.6%), and Klebsiella pneumoniae (4.6%). The identification rate of viridans streptococcus significantly increased from 41.8% in 2013-2017 to 60.9% in 2018-2022. Viridans streptococcus showed an antibiotic sensitivity of 80.5% to ampicillin; the sensitivity to penicillin antibiotics decreased over the study period. Antibiotic susceptibility was approximately 94% for third-generation cephalosporins. K. pneumoniae, which was identified at a high percentage in patients with deep neck space infection, showed increasing antibiotic resistance to most antibiotics over the study period. Conclusion: Viridans streptococcus was identified in head and neck fascial space abscesses with the highest frequency. Empirical antibiotics should be effective against this strain; penicillin antibiotics are considered inappropriate. For effective treatment of deep neck space abscesses, bacterial culture and antibiotic sensitivity tests performed as soon as possible are essential.

Characterization of Salmonella species from poultry slaughterhouses in South Korea: carry-over transmission of Salmonella Thompson ST292 in slaughtering process

  • Yewon Cheong;Jun Bong Lee;Se Kye Kim;Jang Won Yoon
    • Journal of Veterinary Science
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    • v.25 no.3
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    • pp.39.1-39.11
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    • 2024
  • Importance: Salmonella outbreaks linked to poultry meat have been reported continuously worldwide. Therefore, Salmonella contamination of poultry meats in slaughterhouses is one of the critical control points for reducing disease outbreaks in humans. Objective: This study examined the carry-over contamination of Salmonella species through the entire slaughtering process in South Korea. Methods: From 2018 to 2019, 1,097 samples were collected from the nine slaughterhouses distributed nationwide. One hundred and seventeen isolates of Salmonella species were identified using the invA gene-specific polymerase chain reaction, as described previously. The serotype, phylogeny, and antimicrobial resistance of isolates were examined. Results: Among the 117 isolates, 93 were serotyped into Salmonella Mbandaka (n = 36 isolates, 30.8%), Salmonella Thompson (n = 33, 28.2%), and Salmonella Infantis (n = 24, 20.5%). Interestingly, allelic profiling showed that all S. Mbandaka isolates belonged to the lineage of the sequence type (ST) 413, whereas all S. Thompson isolates were ST292. Moreover, almost all S. Thompson isolates (97.0%, 32/33 isolates) belonging to ST292 were multidrug-resistant and possessed the major virulence genes whose products are required for full virulence. Both serotypes were distributed widely throughout the slaughtering process. Pulsed-field gel electrophoretic analysis demonstrated that seven S. Infantis showed 100% identities in their phylogenetic relatedness, indicating that they were sequentially transmitted along the slaughtering processes. Conclusions and Relevance: This study provides more evidence of the carry-over transmission of Salmonella species during the slaughtering processes. ST292 S. Thompson is a potential pathogenic clone of Salmonella species possibly associated with foodborne outbreaks in South Korea.