Eliminating the tigecycline resistance RND efflux pump gene cluster tmexCD-toprJ in bacteria using CRISPR/Cas9.

Objectives: Tigecycline, a last-resort antibiotic in the tetracycline class, has been effective in treating infections caused by multidrug-resistant bacteria. However, the emergence of the tigecycline resistance gene cluster tmexCD-toprJ, which encodes a resistance-nodulation-division efflux pump, has significantly limited its therapeutic effectiveness. This study aims to explore the potential of CRISPR/Cas9-based plasmids to target and cleave tmexCD-toprJ gene cluster from bacterial plasmids and chromosomal integrative conjugative elements (ICEs), respectively.

Development of Phloroglucinol-Linked Tris-Quaternary Ammonium Salt Antimicrobial Peptide Mimics with Low Cytotoxicity and Broad-Spectrum Antibacterial Activity.

Encouraged by the significantly different toxicities and antibacterial activities of diverse linkers, such as alkyl and aromatic nuclei linkers, and the unique structure of phloroglucinol, we synthesized a series of tris-quaternary ammonium salt (tris-QAS) antibacterial peptide mimics based on the marketed drug phloroglucinol. Among them, displayed excellent activity against (MIC = 0.5 μg/mL) and high selectivity (SI > 2560).

Discovery of novel BfmR inhibitors restoring carbapenem susceptibility against carbapenem-resistant by structure-based virtual screening and biological evaluation.

The emergence and spread of pose a severe threat to public health, highlighting the urgent need for the next generation of therapeutics due to its increasing resistance to existing antibiotics. BfmR, a response regulator modulating virulence and antimicrobial resistance, shows a promising potential as a novel antimicrobial target. Developing BfmR inhibitors may propel a new therapeutic direction for intractable infection of resistant strains.

Plant Flavonoids with Antimicrobial Activity against Methicillin-Resistant (MRSA).

Methicillin-resistant (MRSA) has become a serious threat to human public health and global economic development, and there is an urgent need to develop new antimicrobial agents. Flavonoids are the largest group of plant secondary metabolites, and the anti- and anti-MRSA activities of flavonoids have now been widely reported. The aim of this Review is to describe plant-derived flavonoid active ingredients and their effects and mechanisms of inhibitory activity against MRSA in order to provide insights for screening novel antimicrobial agents.

A membrane-targeting magnolol derivative for the treatment of methicillin-resistant infections.

Multidrug-resistant bacterial infections are a major global health challenge, especially the emergence and rapid spread of methicillin-resistant (MRSA) urgently require alternative treatment options. Our study has identified that a magnolol derivative as a promising agent with significant antibacterial activity against and clinical MRSA isolates (MIC = 2-8 μg/mL), showing high membrane selectivity. Unlike traditional antibiotics, demonstrated rapid bactericidal efficiency and a lower propensity for inducing bacterial resistance.

Novel natural osthole-inspired amphiphiles as membrane targeting antibacterials against methicillin-resistant Staphylococcus aureus (MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) is a widespread pathogen causing clinical infections and is multi-resistant to many antibiotics, making it urgent need to develop novel antibacterials to combat MRSA. Herein, we designed and prepared a series of novel osthole amphiphiles 6a-6ad by mimicking the structures and function of antimicrobial peptides (AMPs). Antibacterial assays showed that osthole amphiphile 6aa strongly inhibited S.

Correction: Antimicrobial peptide-modified silver nanoparticles for enhancing the antibacterial efficacy.

[This corrects the article DOI: 10.1039/D0RA05640E.].

Development of Membrane-Targeting Fluorescent 2-Phenyl-1-phenanthro[9,10-]imidazole-Antimicrobial Peptide Mimic Conjugates against Methicillin-Resistant .

The escalation of multidrug-resistant bacterial infections, especially infections caused by methicillin-resistant (MRSA), underscores the urgent need for novel antimicrobial drugs. Here, we synthesized a series of amphiphilic 2-phenyl-1-phenanthro[9,10-]imidazole-antimicrobial peptide (AMP) mimic conjugates (-). Among them, compound exhibited excellent antibacterial activity against G+ bacteria and clinical MRSA isolates (MIC = 0.

Design, synthesis and antibacterial evaluation of low toxicity amphiphilic-cephalosporin derivatives.

Global public health is facing a serious problem as a result of the rise in antibiotic resistance and the decline in the discovery of new antibiotics. In this study, two series of amphiphilic-cephalosporins were designed and synthesized, several of which showed good antibacterial activity against both Gram-positive and Gram-negative bacteria. Structure-activity relationships indicated that the length of the hydrophobic alkyl chain significantly affects the antibacterial activity against Gram-negative bacteria.

Novel membrane-targeting isoxanthohumol-amine conjugates for combating methicillin-resistant Staphylococcus aureus (MRSA) infections.

Methicillin-resistant Staphylococcus aureus (MRSA) is a widespread pathogen causing clinical infections and is multi-resistant to many antibiotics, making it urgent need to develop novel antibacterials to combat MRSA. Here, a series of novel isoxanthohumol-amine conjugates were synthesized as antibacterials. After bioactivity evaluation, a compound E2 was obtained, which showed excellent antibacterial activity against S.

Effective ciprofloxacin cationic antibacterial agent against persister bacteria with low hemolytic toxicity.

With the widespread use of antibiotics, bacterial resistance has developed rapidly. To make matters worse, infections caused by persistent bacteria and biofilms often cannot be completely eliminated, which brings great difficulties to clinical medication. In this work, three series of quinolone pyridinium quaternary ammonium small molecules were designed and synthesized.

Revealing active constituents within traditional Chinese Medicine used for treating bacterial pneumonia, with emphasis on the mechanism of baicalein against multi-drug resistant Klebsiella pneumoniae.

Ethnopharmacological Relevance: The emergence of antibiotic-resistant bacteria has rendered it more challenging to treat bacterial pneumonia. Traditional Chinese medicine (TCM) has superior efficacy in the treatment of pneumonia, and it has the unique advantage of antibacterial resistance against multi-drug resistant (MDR) bacteria, but the medication rule and pharmacological mechanism of its antibacterial activity are not clear.

Aim Of The Study: This study aims to reveal Chinese medication patterns in treating bacterial pneumonia to select bioactive constituents in core herbs, predict their pharmacological mechanisms and further explore their antibacterial ability against clinically isolated MDR Klebsiella pneumoniae (KP) and their antibacterial mechanisms.

Liposomal Antibiotic Booster Potentiates Carbapenems for Combating NDMs-Producing Escherichia coli.

Infections caused by Enterobacterales producing New Delhi Metallo-β-lactamases (NDMs), Zn(II)-dependent enzymes hydrolyzing carbapenems, are difficult to treat. Depriving Zn(II) to inactivate NDMs is an effective solution to reverse carbapenems resistance in NDMs-producing bacteria. However, specific Zn(II) deprivation and better bacterial outer membrane penetrability in vivo are challenges.

Discovery of 2-Aminothiazole-4-carboxylic Acids as Broad-Spectrum Metallo-β-lactamase Inhibitors by Mimicking Carbapenem Hydrolysate Binding.

Metallo-β-lactamases (MBLs) are zinc-dependent enzymes capable of hydrolyzing all bicyclic β-lactam antibiotics, posing a great threat to public health. However, there are currently no clinically approved MBL inhibitors. Despite variations in their active sites, MBLs share a common catalytic mechanism with carbapenems, forming similar reaction species and hydrolysates.

Conjugative plasmids facilitate the transmission of tmexCD2-toprJ2 among carbapenem-resistant Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great threat to global public health. The emergence of tmexCD-toprJ greatly weakened the efficacy of tigecycline in the treatment of CRKP infections. In this study, we did a comprehensive investigation of the prevalence and genomic features of tmexCD-toprJ in clinical CRKP from 2018 to 2020 in Henan province, China.

Identification of tmexC3-tmexD3-toprJ1b in an XDR Providencia rettgeri clinical isolate co-producing NDM-1 and OXA-10 carbapenemases.

Objectives: Emergence of carbapenemase and tigecycline resistance genes in pathogens threatens the efficacy of last-resort antibiotics. High attention should be paid to the spread and convergence of such resistance genes. This study reports an extensively drug-resistant (XDR) Providencia rettgeri clinical strain co-harbouring carbapenemase genes bla, bla and the tmexCD3-toprJ1b gene cluster.

Development of Aromatic-Linked Diamino Acid Antimicrobial Peptide Mimics with Low Hemolytic Toxicity and Excellent Activity against Methicillin-Resistant (MRSA).

Infections caused by methicillin-resistant (MRSA) have become one of the biggest threats to public health. To develop new antibacterial agents against MRSA, a series of diamino acid compounds with aromatic nuclei linkers were designed and synthesized. Compound , which exhibited low hemolytic toxicity and the best selectivity against (SI > 2000), showed good activity against clinical MRSA isolates (MIC = 0.

New insights into the non-enzymatic function of HDAC6.

Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that contains two catalytic domains and a zinc-finger ubiquitin binding domain (ZnF-UBP) domain. The deacetylation function of HDAC6 has been extensively studied with common substrates such as α-tubulin, cortactin, and Hsp90. Apart from its deacetylase activity, HDAC6 ZnF-UBP binds to unanchored ubiquitin of specific sequences and serves as a carrier for transporting aggregated proteins.

Characterization of a Conjugative Hybrid Plasmid Coharboring and in a Klebsiella quasipneumoniae Clinical Isolate.

Generation of hybrid MDR plasmids accelerated the evolution and transmission of resistance genes. In this study, we characterized a - and -coharboring conjugative hybrid plasmid constituted of an IncHI5 plasmid-like region, an IncFII(Yp)/IncFIA plasmid-like region, and a KPN1344 chromosome-like region from a clinical ST852-KL18 Klebsiella quasipneumoniae strain. The gene was captured by a novel integron In, and the gene was located on a new non-Tn group I NTE element.

Discovery of Amphiphilic Xanthohumol Derivatives as Membrane-Targeting Antimicrobials against Methicillin-Resistant .

Infections caused by multidrug-resistant (MDR) bacteria are increasing worldwide, and with limited clinically available antibiotics, it is urgent to develop new antimicrobials to combat these MDR bacteria. Here, a class of novel amphiphilic xanthohumol derivatives were prepared using a building-block approach. Bioactivity assays showed that the molecule not only exhibited a remarkable antibacterial effect against clinical methicillin-resistant (MRSA) isolates (MICs: 1-2 μg/mL) but also had the advantages of rapid bactericidal properties, low toxicity, good plasma stability, and not readily inducing bacterial resistance.

Development of biaromatic core-linked antimicrobial peptide mimics: Substituent position significantly affects antibacterial activity and hemolytic toxicity.

The development of bacterial resistance to the majority of clinically significant antimicrobials has made it more difficult to treat bacterial infections with conventional antibiotics. As part of ongoing research on antimicrobial peptide mimetics, a series of quaternary ammonium cationic compounds with various linkers were designed and synthesized, with some demonstrating high antibacterial activity against Gram-negative and Gram-positive bacteria. The structure-activity relationship study revealed that the spatial position of substituents had a significant impact on antibacterial activity and hemolytic toxicity.

Antibacterial efficacy evaluation and mechanism probe of small lysine chalcone peptide mimics.

Bacterial resistance is a growing threat to public health and a significant barrier to anti-infective treatment. Consequently, the development of novel antibacterial strategies to address this issue is critical. Herein, we developed a series of chalcone-alkyl-lysine compounds by mimicking the chemical structure and antibacterial properties of cationic antimicrobial peptides.