ABSTRACT Biofilms cause up to 80% of infections and are difficult treat due their substantial multidrug resistance compared planktonic counterparts. Based on the observation that human peptide LL-37 is able block biofilm formation at concentrations below its MIC, we screened for small peptides with antibiofilm activity identified novel synthetic cationic 1037 only 9 amino acids in length. Peptide had very weak antimicrobial activity, but 1/30th MIC was effectively prevent (>50% reduction...

Active efflux of antimicrobial agents is a primary mechanism by which bacterial pathogens can become multidrug resistant. The combined use pump inhibitors (EPIs) with substrates under exploration to overcome efflux-mediated resistance. Phenylalanine-arginine β-naphthylamide (PAβN) well-studied EPI that routinely fluoroquinolone antibiotics, but few studies have assessed its utility in combination β-lactam antibiotics. initial goal this study was assess the efficacy β-lactams PAβN against...

Novel cationic antimicrobial peptides typified by structures such as KKKKKKAAXAAWAAXAA-NH2, where X = Phe/Trp, and several of their analogues display high activity against a variety bacteria but exhibit no hemolytic even at dose levels in mammalian erythrocytes. To elucidate mechanism action source selectivity for bacterial membranes, phospholipid mixtures mimicking the compositions natural membranes (containing anionic lipids) zwitterionic lipids + cholesterol) were challenged with...

Abstract The coronavirus disease 2019 (COVID-19) pandemic and antimicrobial resistance (AMR) are parallel interacting health emergencies that provide the opportunity for mutual learning. As their measures consequences comparable, COVID-19 helps to illustrate potential long-term impact of AMR, which is less acute but not crucial. They may also each other as there a push use existing antimicrobials treat critically ill patients in absence specific treatments. Attempts manage spread lead...

Type IV pili (T4P) contain hundreds of major subunits, but minor subunits are also required for assembly and function. Here we show that Pseudomonas aeruginosa pilins prime pilus traffic the pilus-associated adhesin anti-retraction protein, PilY1, to cell surface. PilV, PilW, PilX require PilY1 inclusion in surface vice versa, suggestive complex formation. PilE requires PilVWXY1 inclusion, suggesting it binds a novel interface created by two or more components. FimU is incorporated...

Abstract Type IVa pili are protein filaments essential for virulence in many bacterial pathogens; they extend and retract from the surface of cells to pull bacteria forward. The motor ATPase PilB powers pilus assembly. Here we report structures core domains Geobacter metallireducens bound ADP non-hydrolysable ATP analogue, AMP-PNP, at 3.4 2.3 Å resolution, respectively. These reveal important differences nucleotide binding between chains. Analysis these reveals sequential turnover...

A systematic genetic analysis was performed to identify the inner membrane proteins essential for type IV pilus (T4P) expression in Pseudomonas aeruginosa. By inactivating retraction aspect of function, genes T4P assembly were discriminated. In contrast previous studies system Neisseria spp., we found that components subcomplex consisting PilMNOP not surface expression, whereas highly conserved protein PilC essential. Here, present data may coordinate activity cytoplasmic polymerization...

ABSTRACT Pseudomonas aeruginosa type IV pili (T4P) are virulence factors that promote infection of cystic fibrosis and immunosuppressed patients. As the absence T4P impairs colonization, they attractive targets for development novel therapeutics. Genes in pilMNOPQ operon important both assembly a form bacterial movement, called twitching motility, is required pathogenicity. The II membrane proteins, PilN PilO, dimerize via their periplasmic domains anchor this complex inner membrane. Our...

Urinary tract infections (UTIs) are a problem worldwide, affecting almost half billion people each year. Increasing antibiotic resistance and limited therapeutic options have led to the exploration of alternative therapies for UTIs, including bacteriophage (phage) therapy. This systematic review aims at evaluating efficacy phage therapy in treating UTIs. We employed comprehensive search strategy any language, animal, publication date. A total 55 vivo clinical studies were included. Of...

Under static growth conditions, hyperpiliated, nontwitching pilT and pilU mutants of Pseudomonas aeruginosa formed dense biofilms, showing that adhesion, not twitching motility, is necessary for biofilm initiation. flow the mutant mushroom-like structures larger than those wild type but was defective in formation. Therefore, motility affects development structure, possibly through modulation detachment.

Type IV pili (TFP) are important colonization factors of the opportunistic pathogen Pseudomonas aeruginosa , involved in biofilm formation and attachment to host cells. This study undertook a comprehensive analysis TFP alleles more than 290 environmental, clinical, rectal cystic fibrosis (CF) isolates P. . Based on results, new system nomenclature is proposed, which divided into five distinct phylogenetic groups. Each pilin allele stringently associated with characteristic, accessory genes...

Pseudomonas aeruginosa co‐expresses A‐band lipopolysaccharide (LPS), a homopolymer of rhamnose, and B‐band LPS, heteropolymer with repeating unit 2–5 sugars which is the serotype‐specific antigen. The gene clusters for A‐ biosynthesis in P. O5 (strain PAO1) have been cloned previously. Here we report DNA sequence molecular analysis O‐antigen biosynthetic cluster. Sixteen open reading frames (ORFs) thought to be involved synthesis O antigen were identified, including wzz ( rol ), wzy rfc wbpA...

Beta-lactamases, which evolved from bacterial penicillin-binding proteins (PBPs) involved in peptidoglycan (PG) synthesis, confer resistance to beta-lactam antibiotics. While investigating the genetic basis of biofilm development by Pseudomonas aeruginosa, we noted that plasmid vectors encoding common beta-lactamase marker TEM-1 caused defects twitching motility (mediated type IV pili), adherence and formation without affecting growth rates. Similarly, strains Escherichia coli carrying...

The opportunistic pathogen Pseudomonas aeruginosa expresses polar type IV pili (TFP), which are responsible for adhesion to various materials and twitching motility on surfaces. Twitching occurs by alternate extension retraction of TFP, arise from assembly disassembly pilin subunits at the base pilus. ATPase PilB promotes assembly, while PilT or PilU both promote dissociation. Fluorescent fusions two three ATPases (PilT PilU) were functional, as shown complementation corresponding mutants....

Type IV pili are retractable protein fibres used by many bacterial pathogens for adherence, twitching motility, biofilm development and host colonization. In Pseudomonas aeruginosa, PilB PilT bipolar proteins belonging to the secretion NTPase superfamily, power pilus extension retraction, respectively, while unipolar paralogue PilU supports retraction in an unknown manner. Assay of purified 6×His-tagged PilB, from P. aeruginosa showed that all three have ATPase activities vitro. Conserved...