Grand challenge of antibiotics resistance: A global, multidisciplinary effort is needed

Xie, Jianping

doi:10.3389/frabi.2022.984076

Cited by 3 publications

(4 citation statements)

References 25 publications

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“…The overuse of antibiotics, as well as the decreasing number of antimicrobials approved for clinical use, only contributes to the further distribution of MDR pathogens. This problem stimulates the search for alternative sources of antimicrobial compounds [2].…”

Section: Introductionmentioning

confidence: 99%

Bioengineering the Antimicrobial Activity of Yeast by Recombinant Thanatin Production

Pipiya,

Kudzhaev,

Mirzoeva

et al. 2023

Antibiotics

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The global spread of antibiotic resistance marks the end of the era of conventional antibiotics. Mankind desires new molecular tools to fight pathogenic bacteria. In this regard, the development of new antimicrobials based on antimicrobial peptides (AMPs) is again of particular interest. AMPs have various mechanisms of action on bacterial cells. Moreover, AMPs have been reported to be efficient in preclinical studies, demonstrating a low level of resistance formation. Thanatin is a small, beta-hairpin antimicrobial peptide with a bacterial-specific mode of action, predetermining its low cytotoxicity toward eukaryotic cells. This makes thanatin an exceptional candidate for new antibiotic development. Here, a microorganism was bioengineered to produce an antimicrobial agent, providing novel opportunities in antibiotic research through the directed creation of biocontrol agents. The constitutive heterologous production of recombinant thanatin (rThan) in the yeast Pichia pastoris endows the latter with antibacterial properties. Optimized expression and purification conditions enable a high production level, yielding up to 20 mg/L of rThan from the culture medium. rThan shows a wide spectrum of activity against pathogenic bacteria, similarly to its chemically synthesized analogue. The designed approach provides new avenues for AMP engineering and creating live biocontrol agents to fight antibiotic resistance.

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Section: Introductionmentioning

confidence: 99%

Bioengineering the Antimicrobial Activity of Yeast by Recombinant Thanatin Production

Pipiya,

Kudzhaev,

Mirzoeva

et al. 2023

Antibiotics

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“…It is now well established that the increasing resistance of pathogenic bacteria to various antibiotics poses a concerning threat to the effective treatment of bacterial disease worldwide [1,2]. Resistant bacterial strains continue to appear and spread, one example being the recent detection of a strain of Neisseria gonorrhea in the United States with reduced susceptibility to all the available antibiotics normally used for treatment [3], highlighting the urgent need for alternative treatments.…”

Section: Introductionmentioning

confidence: 99%

An Update Review of Approaches to Multiple Action-Based Antibacterials

Bremner

2023

Antibiotics

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Many approaches are being pursued to address the major global health challenge posed by the increasing resistance of pathogenic bacteria to antibacterial agents. One of the promising approaches being investigated includes the design and development of multiple action-based small-molecule antibacterials. Aspects of this broad area have been reviewed previously, and recent developments are addressed in this update review covering the literature mainly over the past three years. Considerations encompassing drug combinations, single-molecule hybrids and prodrugs are summarised in regard to the intentional design and development of multiple-action agents with a focus on potential triple or greater activities in bacteria. The hope for such single agents or combinations of single agents is that resistance development will be significantly hindered, and they may be useful in tackling bacterial disease caused by both resistant and non-resistant bacteria.

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“…[2] The primary reason for the occurrence of resistance in living beings are the continuous mutations taking place in the affecting organism which ultimately culminates in human mortality. [3] Pharmacological layout uplifts the endless hunt for the newer derivatives against the microorganisms. Despite this fact, innumerable bids have been done in the same discipline, nevertheless the substituted benzimidazole derivatives have come out as the promising and potential candidate processing the sustained capacity for the inhibition of microbial growth.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, certain projects have been established and allocated for the fabrication of the novel antibiotic molecules to deescalate the developing resistance in the body due to the other available drug compounds [2] . The primary reason for the occurrence of resistance in living beings are the continuous mutations taking place in the affecting organism which ultimately culminates in human mortality [3] . Pharmacological layout uplifts the endless hunt for the newer derivatives against the microorganisms.…”

Section: Introductionmentioning

confidence: 99%

Benzimidazol‐1‐yl‐1‐phenylpropanone Analogs as Potent Antimicrobial Agents: Rational Design and Synthesis

Babbar

Swikriti

Saini

et al. 2023

Chemistry & Biodiversity

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Designed, synthesized a sequence of novel benzimidazol‐1‐yl‐1‐phenylpropanone hybrids and assessed for in vitro antimicrobial potential counter to several bacterial strains. Computational Methodology was carried out for designing of the target molecules and structures were confirmed by spectroscopic analysis. Amid the 12 integrated derivatives, (3‐(2‐((3‐fluorobenzylidene)amino)‐1H‐benzo[d]imidazol‐1‐yl)‐1‐phenylpropan‐1‐one (6g) and 3‐(2‐((4‐fluorobenzylidene)amino)‐1H‐benzo[d]imidazol‐1‐yl)‐1‐phenylpropan‐1‐one (6k) were found to acquire excellent antibacterial activity against all bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus), whereas derivative 3‐(2‐((2‐fluorobenzylidene)amino)‐1H‐benzo[d]imidazol‐1‐yl)‐1‐phenylpropan‐1‐one (6c), was potent against Escherichia coli, Bacillus subtilis, Staphylococcus aureus and displayed moderate action against P. aeruginosa. Derivatives with NO2 substituent at 3rd and 4th position, 3‐(2‐((3‐nitroobenzylidene)amino)‐1H‐benzo[d]imidazol‐1‐yl)‐1‐phenylpropan‐1‐one (6h) and 3‐(2‐((4‐nitroobenzylidene)amino)‐1H‐benzo[d]imidazol‐1‐yl)‐1‐phenylpropan‐1‐one (6 l) respectively declared good to moderate results against all bacterial strains. Further, 3‐(2‐((3‐chlorobenzylidene)amino)‐1H‐benzo[d]imidazol‐1‐yl)‐1‐phenylpropan‐1‐one (6f) and 3‐(2‐((4‐chlorobenzylidene)amino)‐1H‐benzo[d]imidazol‐1‐yl)‐1‐phenylpropan‐1‐one (6j) were found to be more competent against both fungal strains (C. albicans, A. niger). Serial two‐fold dilution method was used for the entire study and standard drugs utilized were ciprofloxacin and clotrimazole. MIC values (μg/ml) of novel synthesized analogs were reported in comparison to standard drugs for antibacterial and antifungal actions. Molecular docking studies showed that designed molecules dynamically bound with effective area of the receptor (DNA gyrase B, Clotrimazole complex of cytochrome P 45046A1) and in vitro results were in accord with in silico studies.

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Grand challenge of antibiotics resistance: A global, multidisciplinary effort is needed

Cited by 3 publications

References 25 publications

Bioengineering the Antimicrobial Activity of Yeast by Recombinant Thanatin Production

Bioengineering the Antimicrobial Activity of Yeast by Recombinant Thanatin Production

An Update Review of Approaches to Multiple Action-Based Antibacterials

Benzimidazol‐1‐yl‐1‐phenylpropanone Analogs as Potent Antimicrobial Agents: Rational Design and Synthesis

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