Antimicrobial Activities and Antibiotic Resistance of Nocardiopsis alba Isolated From the Saline Habitats of Coastal Gujarat

Background: : The appearance of antibiotic resistance caused by metallo-β-lactamases (MβLs) is a global public health threat. Developing MβLs inhibitor is an effective way to overcome antibiotic resistance. Recently, azolylthioacetamides were reported to be promising MβLs inhibitors. Methods:: Triazolylthioacetamides were synthesized and tested for inhibition activity against the purified MβL IMP-1. Antimicrobial activities of these inhibitors in combination with cefazolin were evaluated. Isothermal titration calorimetry (ITC) was employed to characterize the binding of the inhibitor to IMP-1, and their action mechanism was studied by molecular docking. Results and Discussion: : Twenty compounds exhibited specific inhibitory activity against IMP-1 with an IC50 value in the range of 3.1-62.5 μM. Eight of the compounds can restore the antibacterial efficacy of cefazolin against E. coli BL21 strain producing IMP-1 by 2-4 fold. ITC monitoring showed that 1c exhibited dose-dependent inhibition on IMP-1. Docking studies revealed that the triazole group in 1c and 2d played an essential role in the inhibition activity. Cytotoxicity assay showed that 1c and 2d have low toxicity in L929 mouse fibroblastic cells. Conclusion: : The triazolylthioacetamides are efficient inhibitors of IMP-1 in vitro and in vivo.

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The Missing Piece: Recent Approaches Investigating the Antimicrobial Mode of Action of Essential Oils

Evolutionary Bioinformatics ◽

10.1177/1176934320938391 ◽

2021 ◽

Vol 17 ◽

pp. 117693432093839

Author(s):

Shun-Kai Yang ◽

Ngai-Paing Tan ◽

Chun-Wie Chong ◽

Aisha Abushelaibi ◽

Swee-Hua-Erin Lim ◽

...

Keyword(s):

Antibiotic Resistance ◽

Essential Oils ◽

Mode Of Action ◽

Plant Secondary Metabolites ◽

Antimicrobial Effect ◽

Underlying Mechanism ◽

Antimicrobial Activities ◽

Genomics And Proteomics ◽

Global Health Issue ◽

Hospital Stays

Antibiotic resistance is a major global health issue that has seen alarming rates of increase in all parts of the world over the past two decades. The surge in antibiotic resistance has resulted in longer hospital stays, higher medical costs, and elevated mortality rates. Constant attempts have been made to discover newer and more effective antimicrobials to reduce the severity of antibiotic resistance. Plant secondary metabolites, such as essential oils, have been the major focus due to their complexity and bioactive nature. However, the underlying mechanism of their antimicrobial effect remains largely unknown. Understanding the antimicrobial mode of action of essential oils is crucial in developing potential strategies for the use of essential oils in a clinical setting. Recent advances in genomics and proteomics have enhanced our understanding of the antimicrobial mode of action of essential oils. We might well be at the dawn of completing a mystery on how essential oils carry out their antimicrobial activities. Therefore, an overview of essential oils with regard to their antimicrobial activities and mode of action is discussed in this review. Recent approaches used in identifying the antimicrobial mode of action of essential oils, specifically from the perspective of genomics and proteomics, are also synthesized. Based on the information gathered from this review, we offer recommendations for future strategies and prospects for the study of essential oils and their function as antimicrobials.

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Evaluation of Antimicrobial Activity of Extracts of Terminalia chebula and Piper nigrum against Streptococcus mutans: An In Vitro Study

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i36a31944 ◽

2021 ◽

pp. 218-224

Author(s):

Pavani Bellamkonda ◽

Ramesh Kumar Koothati ◽

Aamina Bee ◽

Abhishree Desai ◽

G. K. Aarthi ◽

...

Keyword(s):

Antimicrobial Activity ◽

Antibiotic Resistance ◽

In Vitro Study ◽

Antimicrobial Activities ◽

Diffusion Method ◽

Piper Nigrum ◽

Terminalia Chebula ◽

Bacterial Strains ◽

Antimicrobial Potency

Objective: Dental caries is an infectious disease in which S. mutans plays a key role. Haphazard and irrational use of antibiotics leads to antibiotic resistance and fatal diarrhoeal diseases in children. Antimicrobial potency of Terminalia chebula and Piper nigrum extracts against several bacterial strains have been documented. The aims of this study were to assess and compare the antimicrobial activities of T. chebula and P. nigrum extracts against S. mutans with Ciprofloxacin as the positive control. Materials and Methods: For this purpose, S. mutans was isolated from plaque samples of people with active caries lesions. Antimicrobial potency of both T. chebula and P.nigrum were tested using agar well diffusion method. Results: All the tested extracts showed antibacterial activity against S. mutans bacteria. Regarding the two tested herbs extracts, a higher antimicrobial activity was shown by the methanol extract of T. chebula with a mean diameter of inhibition zone was 26.75mm and a minimum inhibitory concentration (MIC) at 25mg /ml concentration followed by acetonic extract. Conclusion: These findings confirm the Antimicrobial potency of T. chebula which can be used as an alternative antibiotic and/or in combination with allopathic antibiotics to prevent the antibiotic resistance.

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Symmetrical Modification of Minimized Dermaseptins to Extend the Spectrum of Antimicrobials with Endotoxin Neutralization Potency

International Journal of Molecular Sciences ◽

10.3390/ijms20061417 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1417 ◽

Cited By ~ 6

Author(s):

Changxuan Shao ◽

Weizhong Li ◽

Peng Tan ◽

Anshan Shan ◽

Xiujing Dou ◽

...

Keyword(s):

Antibacterial Activity ◽

Antibiotic Resistance ◽

Multidrug Resistance ◽

Broad Spectrum ◽

Antimicrobial Agents ◽

Therapeutic Index ◽

Antimicrobial Activities ◽

Effective Strategy ◽

Gram Negative ◽

Gram Positive Bacteria

Antimicrobial peptides (AMPs) have emerged as a promising class of antimicrobial agents that could potentially address the global antibiotic resistance. Generating mirror-like peptides by minimizing dermaseptin family sequences is an effective strategy for designing AMPs. However, the previous research still had some limitations such as lower effectiveness and a narrow spectrum of antibacterial activity. To further expand and hone this strategy, we designed a series of AMPs consisting of the WXMXW-NH2 motif (X represents V, I, F, and W; M represents KAAAKAAAK). The peptides formed α-helices and displayed broad-spectrum antimicrobial activities against eleven types of clinical bacteria including both Gram-negative and Gram-positive bacteria. The optimized peptide WW exhibited high physical rupture by inducing membrane shrinkage, disruption, and lysis. Moreover, WW effectively neutralized endotoxins and inhibited the inflammatory response while having the highest therapeutic index. In conclusion, these results indicated that the peptide WW has potential as a broad-spectrum antimicrobial agent or preservative for overcoming the risk of multidrug resistance in localized or external therapeutic applications.

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Ceragenins and antimicrobial peptides kill bacteria through distinct mechanisms

10.1101/2020.10.20.346411 ◽

2020 ◽

Author(s):

Gabriel Mitchell ◽

Melanie R. Silvis ◽

Kelsey C. Talkington ◽

Jonathan M. Budzik ◽

Claire E. Dodd ◽

...

Keyword(s):

Antibiotic Resistance ◽

Antimicrobial Peptides ◽

Mode Of Action ◽

Essential Gene ◽

Bacterial Species ◽

Antimicrobial Activities ◽

Production Costs ◽

Cationic Antimicrobial Peptides ◽

E Coli ◽

Naturally Occurring

ABSTRACTCeragenins are a family of synthetic amphipathic molecules designed to mimic the properties of naturally-occurring cationic antimicrobial peptides (CAMPs). Although ceragenins have potent antimicrobial activity, whether their mode of action is similar to that of CAMPs has remained elusive. Here we report the results of a comparative study of the bacterial responses to two well-studied CAMPs, LL37 and colistin, and two ceragenins with related structures, CSA13 and CSA131. Using transcriptomic and proteomic analyses, we found that Escherichia coli responds similarly to both CAMPs and ceragenins by inducing a Cpx envelope stress response. However, whereas E. coli exposed to CAMPs increased expression of genes involved in colanic acid biosynthesis, bacteria exposed to ceragenins specifically modulated functions related to phosphate transport, indicating distinct mechanisms of action between these two classes of molecules. Although traditional genetic approaches failed to identify genes that confer high-level resistance to ceragenins, using a Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) approach we identified E. coli essential genes that when knocked down modify sensitivity to these molecules. Comparison of the essential gene-antibiotic interactions for each of the CAMPs and ceragenins identified both overlapping and distinct dependencies for their antimicrobial activities. Overall, this study indicates that while some bacterial responses to ceragenins overlap with those induced by naturally-occurring CAMPs, these synthetic molecules target the bacterial envelope using a distinctive mode of action.IMPORTANCEThe development of novel antibiotics is essential since the current arsenal of antimicrobials will soon be ineffective due to the widespread occurrence of antibiotic resistance. Development of naturally-occurring cationic antimicrobial peptides (CAMPs) for therapeutics to combat antibiotic resistance has been hampered by high production costs and protease sensitivity, among other factors. The ceragenins are a family of synthetic CAMP mimics that kill a broad spectrum of bacterial species but are less expensive to produce, resistant to proteolytic degradation and have been associated with low levels of resistance. Determining how ceragenins function may identify new essential biological pathways of bacteria that are less prone to development of resistance and will further our understanding of the design principles for maximizing the effects of synthetic CAMPs.

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Structural Features Governing the Activity of Lactoferricin-Derived Peptides That Act in Synergy with Antibiotics againstPseudomonas aeruginosa In VitroandIn Vivo

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00904-10 ◽

2010 ◽

Vol 55 (1) ◽

pp. 218-228 ◽

Cited By ~ 35

Author(s):

Susana Sánchez-Gómez ◽

Bostjan Japelj ◽

Roman Jerala ◽

Ignacio Moriyón ◽

Mirian Fernández Alonso ◽

...

Keyword(s):

Antibiotic Resistance ◽

Efflux Pump ◽

Concomitant Administration ◽

Structural Features ◽

Antimicrobial Activities ◽

Resistance Mechanisms ◽

Multidrug Efflux ◽

Multidrug Efflux Pump ◽

Relationship Analysis ◽

Lethal Infection

ABSTRACTPseudomonas aeruginosais naturally resistant to many antibiotics, and infections caused by this organism are a serious threat, especially to hospitalized patients. The intrinsic low permeability ofP. aeruginosato antibiotics results from the coordinated action of several mechanisms, such as the presence of restrictive porins and the expression of multidrug efflux pump systems. Our goal was to develop antimicrobial peptides with an improved bacterial membrane-permeabilizing ability, so that they enhance the antibacterial activity of antibiotics. We carried out a structure activity relationship analysis to investigate the parameters that govern the permeabilizing activity of short (8- to 12-amino-acid) lactoferricin-derived peptides. We used a new class of constitutional and sequence-dependent descriptors called PEDES (peptidedescriptors fromsequence) that allowed us to predict (Spearman's ρ = 0.74;P< 0.001) the permeabilizing activity of a new peptide generation. To study if peptide-mediated permeabilization could neutralize antibiotic resistance mechanisms, the most potent peptides were combined with antibiotics, and the antimicrobial activities of the combinations were determined onP. aeruginosastrains whose mechanisms of resistance to those antibiotics had been previously characterized. A subinhibitory concentration of compound P2-15 or P2-27 sensitizedP. aeruginosato most classes of antibiotics tested and counteracted several mechanisms of antibiotic resistance, including loss of the OprD porin and overexpression of several multidrug efflux pump systems. Using a mouse model of lethal infection, we demonstrated that whereas P2-15 and erythromycin were unable to protect mice when administered separately, concomitant administration of the compounds afforded long-lasting protection to one-third of the animals.

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