ACS Infectious Diseases最新文献_第3页

Expanding the Landscape of Dual Action Antifolate Antibacterials through 2,4-Diamino-1,6-dihydro-1,3,5-triazines.

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-02-14 DOI: 10.1021/acsinfecdis.4c00768

John D Georgiades, Daniel A Berkovich, Samuel R McKee, Angela R Smith, Banumathi Sankaran, Kelly N Flentie, Carlos H Castañeda, Daniel G Grohmann, Ram Rohatgi, Carrie Lasky, Twila A Mason, James E Champine, Patricia A Miller, Ute Möllmann, Garrett C Moraski, Scott G Franzblau, Marvin J Miller, Christina L Stallings, Joseph M Jez, Bruce A Hathaway, Timothy A Wencewicz

{"title":"Expanding the Landscape of Dual Action Antifolate Antibacterials through 2,4-Diamino-1,6-dihydro-1,3,5-triazines.","authors":"John D Georgiades, Daniel A Berkovich, Samuel R McKee, Angela R Smith, Banumathi Sankaran, Kelly N Flentie, Carlos H Castañeda, Daniel G Grohmann, Ram Rohatgi, Carrie Lasky, Twila A Mason, James E Champine, Patricia A Miller, Ute Möllmann, Garrett C Moraski, Scott G Franzblau, Marvin J Miller, Christina L Stallings, Joseph M Jez, Bruce A Hathaway, Timothy A Wencewicz","doi":"10.1021/acsinfecdis.4c00768","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c00768","url":null,"abstract":"Antibiotics that operate via multiple mechanisms of action are a promising strategy to combat growing resistance. Previous studies have shown that dual action antifolates formed from a pyrroloquinazolinediamine core can inhibit the growth of bacterial pathogens without developing resistance. In this work, we expand the scope of dual action antifolates by repurposing the 2,4-diamino-1,6-dihydro-1,3,5-triazine (DADHT) cycloguanil scaffold to a variety of derivatives designed to inhibit dihydrofolate reductase (DHFR) and disrupt bacterial membranes. Dual mechanism DADHTs have activity against a variety of target pathogens, including Mycobacterium tuberculosis, Mycobacterium abscessus, and Pseudomonas aeruginosa, among other ESKAPEE organisms. Through X-ray crystallography, we confirmed engagement of the Escherichia coli DHFR target and found that some DADHTs stabilize a previously unobserved conformation of the enzyme but, broadly, bind in the occluded conformation. Using in vitro inhibition of purified E. coli and Staphylococcus aureus DHFR and disruption of E. coli membranes, we determined that alkyl substitution of dihydrotriazine at the 6-position best optimizes the DADHT's two mechanisms of action. By employing both mechanisms, the DADHT spectrum of activity was extended beyond the scope of traditional antifolates. We are optimistic that the dual mechanism approach, particularly through the action of antifolates, offers a unique means of combating hard-to-treat bacterial infections.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advantages and Challenges of Using Antimicrobial Peptides in Synergism with Antibiotics for Treating Multidrug-Resistant Bacteria.

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-02-14 Epub Date: 2025-01-24 DOI: 10.1021/acsinfecdis.4c00702

Regina Meneses Gonçalves, Bruna Estéfani Dutra Monges, Karen Garcia Nogueira Oshiro, Elizabete de Souza Cândido, João Pedro Farias Pimentel, Octávio Luiz Franco, Marlon Henrique Cardoso

{"title":"Advantages and Challenges of Using Antimicrobial Peptides in Synergism with Antibiotics for Treating Multidrug-Resistant Bacteria.","authors":"Regina Meneses Gonçalves, Bruna Estéfani Dutra Monges, Karen Garcia Nogueira Oshiro, Elizabete de Souza Cândido, João Pedro Farias Pimentel, Octávio Luiz Franco, Marlon Henrique Cardoso","doi":"10.1021/acsinfecdis.4c00702","DOIUrl":"10.1021/acsinfecdis.4c00702","url":null,"abstract":"Multidrug-resistant bacteria (MDR) have become a global threat, impairing positive outcomes in many cases of infectious diseases. Treating bacterial infections with antibiotic monotherapy has become a huge challenge in modern medicine. Although conventional antibiotics can be efficient against many bacteria, there is still a need to develop antimicrobial agents that act against MDR bacteria. Bioactive peptides, particularly effective against specific types of bacteria, are recognized for their selective and effective action against microorganisms and, at the same time, are relatively safe and well tolerated. Therefore, a growing number of works have proposed the use of antimicrobial peptides (AMPs) in synergism with commercial antibiotics as an alternative therapeutic strategy. This review provides an overview of the critical parameters for using AMPs in synergism with antibiotics as well as addressing the strengths and weaknesses of this combination therapy using in vitro and in vivo models of infection. We also cover the challenges and perspectives of using this approach for clinical practice and the advantages of applying artificial intelligence strategies to predict the most promising combination therapies between AMPs and antibiotics.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"323-334"},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Key Facets for the Elimination of Vector-Borne Diseases Filariasis, Leishmaniasis, and Malaria. 消除媒介传播疾病的关键方面：丝虫病、利什曼病和疟疾。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-02-14 Epub Date: 2025-01-09 DOI: 10.1021/acsinfecdis.4c00431

Rini Chaturvedi, Amit Sharma

引用次数: 0

Stereospecific Resistance to N2-Acyl Tetrahydro-β-carboline Antimalarials Is Mediated by a PfMDR1 Mutation That Confers Collateral Drug Sensitivity. 对n2 -酰基四氢β-卡波林抗疟药的立体特异性耐药是由PfMDR1突变介导的，该突变赋予了附带药物敏感性。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-02-14 Epub Date: 2025-01-14 DOI: 10.1021/acsinfecdis.4c01001

Emily K Bremers, Joshua H Butler, Leticia S Do Amaral, Emilio F Merino, Hanan Almolhim, Bo Zhou, Rodrigo P Baptista, Maxim Totrov, Paul R Carlier, Maria Belen Cassera

{"title":"Stereospecific Resistance to N2-Acyl Tetrahydro-β-carboline Antimalarials Is Mediated by a PfMDR1 Mutation That Confers Collateral Drug Sensitivity.","authors":"Emily K Bremers, Joshua H Butler, Leticia S Do Amaral, Emilio F Merino, Hanan Almolhim, Bo Zhou, Rodrigo P Baptista, Maxim Totrov, Paul R Carlier, Maria Belen Cassera","doi":"10.1021/acsinfecdis.4c01001","DOIUrl":"10.1021/acsinfecdis.4c01001","url":null,"abstract":"Half the world's population is at risk of developing a malaria infection, which is caused by parasites of the genus Plasmodium. Currently, resistance has been identified to all clinically available antimalarials, highlighting an urgent need to develop novel compounds and better understand common mechanisms of resistance. We previously identified a novel tetrahydro-β-carboline compound, PRC1590, which potently kills the malaria parasite. To better understand its mechanism of action, we selected for and characterized resistance to PRC1590 in Plasmodium falciparum. Through in vitro selection of resistance to PRC1590, we have identified that a single-nucleotide polymorphism on the parasite's multidrug resistance protein 1 (PfMDR1 G293V) mediates resistance to PRC1590. This mutation results in stereospecific resistance and sensitizes parasites to other antimalarials, such as mefloquine, quinine, and MMV019017. Intraerythrocytic asexual stage specificity assays have revealed that PRC1590 is most potent during the trophozoite stage when the parasite forms a single digestive vacuole (DV) and actively digests hemoglobin. Moreover, fluorescence microscopy revealed that PRC1590 disrupts the function of the DV, indicating a potential molecular target associated with this organelle. Our findings mark a significant step in understanding the mechanism of resistance and the mode of action of this emerging class of antimalarials. In addition, our results suggest a potential link between resistance mediated by PfMDR1 and PRC1590's molecular target. This research underscores the pressing need for future research aimed at investigating the intricate relationship between a compound's chemical scaffold, molecular target, and resistance mutations associated with PfMDR1.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"529-542"},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Building Spatiotemporal Understanding of Mycobacterium tuberculosis-Host Interactions.

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-02-14 Epub Date: 2025-01-23 DOI: 10.1021/acsinfecdis.4c00840

Anna-Lisa E Lawrence, Shumin Tan

{"title":"Building Spatiotemporal Understanding of Mycobacterium tuberculosis-Host Interactions.","authors":"Anna-Lisa E Lawrence, Shumin Tan","doi":"10.1021/acsinfecdis.4c00840","DOIUrl":"10.1021/acsinfecdis.4c00840","url":null,"abstract":"Heterogeneity during Mycobacterium tuberculosis (Mtb) infection greatly impacts disease outcome and complicates treatment. This heterogeneity encompasses many facets, spanning local differences in the host immune response to Mtb and the environment experienced by the bacterium, to nonuniformity in Mtb replication state. All of these facets are interlinked and each can affect Mtb susceptibility to antibiotic treatment. In-depth spatiotemporal understanding of Mtb-host interactions is thus critical to both fundamental comprehension of Mtb infection biology and for the development of effective therapeutic regimens. Such spatiotemporal understanding dictates the need for analysis at the single bacterium/cell level in the context of intact tissue architecture, which has been a significant technical challenge. Excitingly, innovations in spatial single cell methodology have opened the door to such studies, beginning to illuminate aspects ranging from intergranuloma differences in cellular composition and phenotype, to sublocation differences in Mtb physiology and replication state. In this perspective, we discuss recent studies that demonstrate the potential of these methodological advancements to reveal critical spatiotemporal insight into Mtb-host interactions, and highlight future avenues of research made possible by these advances.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"277-286"},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elucidation of the Glycan Structure of the b-type Flagellin of Pseudomonas aeruginosa PAO1.

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-02-14 Epub Date: 2025-01-24 DOI: 10.1021/acsinfecdis.4c00896

Paul J Hensbergen, Loes van Huijkelom, Jordy van Angeren, Arnoud H de Ru, Bart Claushuis, Peter A van Veelen, Wiep Klaas Smits, Jeroen Corver

{"title":"Elucidation of the Glycan Structure of the b-type Flagellin of Pseudomonas aeruginosa PAO1.","authors":"Paul J Hensbergen, Loes van Huijkelom, Jordy van Angeren, Arnoud H de Ru, Bart Claushuis, Peter A van Veelen, Wiep Klaas Smits, Jeroen Corver","doi":"10.1021/acsinfecdis.4c00896","DOIUrl":"10.1021/acsinfecdis.4c00896","url":null,"abstract":"Flagella are essential for motility and pathogenicity in many bacteria. The main component of the flagellar filament, flagellin (FliC), often undergoes post-translational modifications, with glycosylation being a common occurrence. In Pseudomonas aeruginosa PAO1, the b-type flagellin is O-glycosylated with a structure that includes a deoxyhexose, a phospho-group, and a previous unknown moiety. This structure resembles the well-characterized glycan (Type A) in Clostridioides difficile strain 630, which features an N-acetylglucosamine linked to an N-methylthreonine via a phosphodiester bond. This study aimed to characterize the b-type glycan structure in Pseudomonas aeruginosa PAO1 using a set of mass spectrometry experiments. For this purpose, we used wild-type P. aeruginosa PAO1 and several gene mutants from the b-type glycan biosynthetic cluster. Moreover, we compared the mass spectrometry characteristics of the b-type glycan with those of in vitro modified Type A-peptides from C. difficile strain 630Δerm. Our results demonstrate that the thus far unknown moiety of the b-type glycan in P. aeruginosa consists of an N,N-dimethylthreonine. These data allowed us to refine our model of the flagellin glycan biosynthetic pathway in both P. aeruginosa PAO1 and C. difficile strain 630.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"518-528"},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of the Mobile Active Site Flap in IMP Dehydrogenase Inhibitor Binding.

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-02-14 Epub Date: 2025-01-29 DOI: 10.1021/acsinfecdis.4c00636

Xingyou Wang, Masha M Rosenberg, Youngchang Kim, Natalia Maltseva, Gregory D Cuny, Andrzej Joachimiak, Petr Kuzmič, Lizbeth Hedstrom

{"title":"Role of the Mobile Active Site Flap in IMP Dehydrogenase Inhibitor Binding.","authors":"Xingyou Wang, Masha M Rosenberg, Youngchang Kim, Natalia Maltseva, Gregory D Cuny, Andrzej Joachimiak, Petr Kuzmič, Lizbeth Hedstrom","doi":"10.1021/acsinfecdis.4c00636","DOIUrl":"10.1021/acsinfecdis.4c00636","url":null,"abstract":"Inosine 5'-monophosphate dehydrogenase (IMPDH) is a promising antibiotic target. This enzyme catalyzes the NAD-dependent oxidation of inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP), which is the rate-limiting step in guanine nucleotide biosynthesis. Bacterial IMPDH-specific inhibitors have been developed that bind to the NAD+ site. These inhibitors display varied affinities to different bacterial IMPDHs that are not easily rationalized by X-ray crystal structures of enzyme-inhibitor complexes. Inspection of X-ray crystal structures of 25 enzyme-inhibitor complexes, including 10 newly described, suggested that a mobile active site flap may be a structural determinant of inhibitor potency. Saturation transfer difference NMR experiments also suggested that the flap may contact the inhibitors to varying extents in different IMPDHs. Flap residue Leu413 contacted some inhibitors but was not structured in the crystal structures of other inhibitor complexes. The substitution of Leu413 with Phe or Ala in Bacillus anthracis IMPDH had inhibitor-selective effects, suggesting residue 413 could be a structural determinant of affinity. Curiously, the Ala substitution increased the potency of most inhibitors, even those that contacted Leu413 in the crystal structures. Presteady-state and steady-state kinetics experiments showed that the Leu413Ala substitution had comparable effects on inhibitor binding to the noncovalent E·IMP complex and the covalent intermediate E-XMP*, suggesting that the flap had similar interactions in both complexes. These results demonstrate that contacts do not necessarily indicate favorable interactions, and poorly structured mobile regions should not be discounted when assessing binding determinants.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"442-452"},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unfolding the Potential of Pyrrole- and Indole-Based Allylidene Hydrazine Carboximidamides as Antimicrobial Agents. 揭示吡咯和吲哚基烯丙叉肼甲脒作为抗菌剂的潜力。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-02-14 Epub Date: 2025-01-13 DOI: 10.1021/acsinfecdis.4c00849

Amit Sharma, Sonali J Jain, Prabhat Nath Jha, Santosh Rudrawar, Sandip B Bharate, Hemant R Jadhav

{"title":"Unfolding the Potential of Pyrrole- and Indole-Based Allylidene Hydrazine Carboximidamides as Antimicrobial Agents.","authors":"Amit Sharma, Sonali J Jain, Prabhat Nath Jha, Santosh Rudrawar, Sandip B Bharate, Hemant R Jadhav","doi":"10.1021/acsinfecdis.4c00849","DOIUrl":"10.1021/acsinfecdis.4c00849","url":null,"abstract":"Antimicrobial drug resistance is a significant global health challenge, causing hundreds of thousands of deaths annually and severely impacting healthcare systems worldwide. Several reported antimicrobial compounds have a guanidine motif, as the positive charge on guanidine promotes cell lysis. Therefore, pyrrole- and indole-based allylidene hydrazine carboximidamide derivatives with guanidine motifs are proposed as antimicrobial agents that mimic cationic antimicrobial peptides (CAMPs). A total of 72 derivatives having pyrrol-2-yl-phenyl allylidene hydrazine carboximidamide and indol-3-yl-phenyl allylidene hydrazine carboximidamide scaffolds were assessed for their inhibitory potential against a panel of Gram-positive and Gram-negative bacteria. Analogs 1j, 1k, 1s, 2j, 2q, 4a, 4c, 4h, 5b, 6a, and 6d exhibited potent broad-spectrum antimicrobial activity better than the standard antibiotics. Also, these compounds showed no cytotoxicity up to 3-fold of the minimum inhibitory concentration, and structure-activity relationship was established. Further, the most active compound, 6a, showed a strong biofilm disruption, acted on the bacterial membrane, and lysed it. The further development of these compounds as novel antimicrobial agents is warranted.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"493-505"},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of Human PIM Kinase Inhibitors as a Class of Anthelmintic Drugs to Treat Intestinal Nematode Infections. 人类PIM激酶抑制剂作为一类驱虫剂药物治疗肠道线虫感染的发现。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-02-14 Epub Date: 2025-01-19 DOI: 10.1021/acsinfecdis.4c00864

Victoria Banas, Mostafa A Elfawal, Bruce A Rosa, Matthew Mahoney, Jacquelyn Kauffman, Emily Goetz, Paulina Chen, Raffi V Aroian, Makedonka Mitreva, James W Janetka

{"title":"Discovery of Human PIM Kinase Inhibitors as a Class of Anthelmintic Drugs to Treat Intestinal Nematode Infections.","authors":"Victoria Banas, Mostafa A Elfawal, Bruce A Rosa, Matthew Mahoney, Jacquelyn Kauffman, Emily Goetz, Paulina Chen, Raffi V Aroian, Makedonka Mitreva, James W Janetka","doi":"10.1021/acsinfecdis.4c00864","DOIUrl":"10.1021/acsinfecdis.4c00864","url":null,"abstract":"Soil-transmitted helminth (STH) infections affect one-fourth of the global population and pose a significant threat to human and animal health, with limited treatment options and emerging drug resistance. Trichuris trichiura (whipworm) stands out as a neglected disease, necessitating new drugs to address this unmet medical need. We discovered that several different chemical series of related human Provirus Integration sites for Moloney murine leukemia virus (PIM) family kinase inhibitors possess potent anthelmintic activity by using whole-worm motility assays. Systematic structure-activity relationship (SAR) studies based on the pan-PIM kinase inhibitor CX-6258 were conducted to identify compounds displaying improved in vitro motility inhibition of both adult hookworm (Ancylostoma ceylanicum) and adult whipworm (Trichuris muris) nematodes. A broad kinase selectivity screen of >450 human kinases confirms PIM1 kinase and others as potential targets for CX-6258 and analogues thereof. In addition, we demonstrated that CX-6258 significantly reduced worm burden and egg counts in the T. muris infection model of mice, establishing it as a new oral small molecule anthelmintic therapeutic.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"506-517"},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decoding the Role of Antimicrobial Peptides in the Fight against Mycobacterium tuberculosis.

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-02-14 Epub Date: 2025-01-28 DOI: 10.1021/acsinfecdis.4c00806

Sapna Saini, Sunny Pal, Rashmi Sharma

{"title":"Decoding the Role of Antimicrobial Peptides in the Fight against Mycobacterium tuberculosis.","authors":"Sapna Saini, Sunny Pal, Rashmi Sharma","doi":"10.1021/acsinfecdis.4c00806","DOIUrl":"10.1021/acsinfecdis.4c00806","url":null,"abstract":"Tuberculosis (TB), a leading infectious disease caused by the pathogen Mycobacterium tuberculosis, poses a significant treatment challenge due to its unique characteristics and resistance to existing drugs. The conventional treatment regimens, which are lengthy and involve multiple drugs, often result in poor patient adherence and subsequent drug resistance, particularly with multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. This highlights the urgent need for novel anti-TB therapies and new drug targets. Antimicrobial peptides (AMPs), which are natural host defense molecules present in all living organisms, offer a promising alternative to traditional small-molecule drugs. AMPs have several advantages, including their broad-spectrum activity and the potential to circumvent existing resistance mechanisms. However, their clinical application faces challenges such as stability, delivery, and potential toxicity. This review aims to provide essential information on AMPs, including their sources, classification, mode of action, induction within the host under stress, efficacy against M. tuberculosis, clinical status and hurdles to their use. It also highlights future research directions to address these challenges and advance the development of AMP-based therapies for TB.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"350-365"},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0