Quorum sensing is a chemical communication process that bacteria use to regulate collective behaviors. Disabling quorum-sensing circuits with small molecules has been proposed as potential strategy prevent bacterial pathogenicity. The human pathogen Pseudomonas aeruginosa uses quorum control virulence and biofilm formation. Here, we analyze synthetic for inhibition of the two P. receptors, LasR RhlR. Our most effective compound, meta-bromo-thiolactone (mBTL), inhibits both production factor...

Summary Quantitative spatial distributions of ribosomes (S2‐YFP) and RNA polymerase (RNAP; β′‐yGFP) in live Escherichia coli are measured by superresolution fluorescence microscopy. In moderate growth conditions, nucleoid–ribosome segregation is strong, RNAP localizes to the nucleoid lobes. The mean copy numbers per cell 4600 RNAPs 55 000 ribosomes. Only 10–15% lie within densest part lobes, at most 4% two ribosome‐rich endcaps. predominant observed diffusion coefficient D ribo = 0.04 µm 2 s...

Significance Pseudomonas aeruginosa is a pathogen that kills remarkably wide range of hosts. The environmental cues regulate P. virulence have remained unclear. Here, we develop rapid imaging-based assay to quantify virulence. We find association with rigid surfaces induces toward multiple Virulence induction depends on the mechanical, but not chemical, properties and requires surface-exposed protein PilY1, which has homology mechanosensitive von Willebrand factor A domain. Specific mutation...

Many bacteria possess large numbers of two-component signalling systems, which are composed histidine kinase-response regulator pairs. The high level sequence similarity between some systems raises the possibility undesired cross-talk a kinase and non-cognate response regulator. Although molecular specificity ensures that phospho-transfer occurs primarily correct partners, even low inappropriate could lead to unacceptable levels noise or interference in signal transduction. To explore...

Bacteria inhabit a wide variety of environments in which fluid flow is present, including healthcare and food processing settings the vasculature animals plants. The motility bacteria on surfaces presence has not been well characterized. Here we focus Pseudomonas aeruginosa, an opportunistic human pathogen that thrives conditions such as catheters respiratory tracts. We investigate effects P. aeruginosa cells describe mechanism surface shear stress orients surface-attached along direction,...

We investigate the effect of bacteriophage infection and antibiotic treatment on coordination swarming, a collective form flagellum- pilus-mediated motility in bacteria. show that phage opportunistic bacterial pathogen Pseudomonas aeruginosa abolishes swarming infected subpopulation induces release quinolone signaling molecule PQS, which repulses uninfected subpopulations from approaching area. These mechanisms have overall limiting to subpopulation, promotes survival population. Antibiotic...

Abstract First proposed as antimicrobial agents, histones were later recognized for their role in condensing chromosomes. Histone activity has been reported innate immune responses. However, how kill bacteria remained elusive. The co-localization of with peptides (AMPs) cells suggests that may be part a larger mechanism vivo. Here we report histone H2A enters E. coli and S. aureus through membrane pores formed by the AMPs LL-37 magainin-2. enhances AMP-induced pores, depolarizes bacterial...

The development of new approaches for the treatment antimicrobial-resistant infections is an urgent public health priority. Pseudomonas aeruginosa pathogen, in particular, a leading source infection hospital settings, with few available options. In context effort to develop antivirulence strategies combat bacterial infection, we identified series highly effective small molecules that inhibit production pyocyanin, redox-active virulence factor produced by P. aeruginosa. Interestingly, these...

The rise of antibiotic resistance requires the development new strategies to combat bacterial infection and pathogenesis. A major direction has been drugs that broadly target virulence. However, few targets have identified due species-specific nature many virulence regulators. lack a regulator is conserved across species presented further challenge therapeutics. Here, we identify NADH activity an important role in induction pathogen P. aeruginosa . This finding, coupled with ubiquity...

Understanding bacterial physiology in real-world environments requires noninvasive approaches and is a challenging yet necessary endeavor to effectively treat infectious disease. Bacteria evolve strategies tolerate chemical gradients associated with infections. The DIVER (Deep Imaging Via Enhanced Recovery) microscope can image autofluorescence fluorescence lifetime throughout samples high optical scattering, enabling the study of naturally formed intact biofilms. Using DIVER, long...

We have evolved a robust two‐component signal transduction pathway from sensor kinase (SK) and non‐partner response regulator (RR) that show weak cross‐talk in vitro no detectable vivo wild‐type strains. The SK, CpxA, is bifunctional, with both phosphatase activities for its partner RR. by combining small number of mutations CpxA individually increase phosphorylation the RR OmpR, activity against phospho‐OmpR emerges. resulting circuit also becomes responsive to input CpxA. effects these...

Summary Each P seudomonas aeruginosa cell localizes two types of motility structures, a single flagellum and one or clusters type IV pili, to the poles. Previous studies suggested that these structures arrive at pole through distinct mechanisms. Here we performed swimming screen identify polar localization factors discovered three genes homologous TonB / ExbB ExbD complex have defects in both flagella‐mediated pilus‐mediated twitching motility. We found deletion tonB3 , PA 2983 2982 led...

The mechanical properties of bacteria are important for protecting cells against physical stress. cell wall is the best-characterized cellular element contributing to bacterial mechanics; however, biochemistry underlying its regulation and assembly still not completely understood. Using a unique high-throughput biophysical assay, we identified genes coding proteins that modulate stiffness in opportunistic human pathogen Pseudomonas aeruginosa . This approach enabled us discover with roles...

Previously described selective plane illumination microscopy techniques typically offset ease of use and sample handling for maximum imaging performance or vice versa. Also, to reduce cost complexity while maximizing flexibility, it is highly desirable implement light sheet such that can be added a standard research microscope instead setting up dedicated system. We devised new approach termed sideSPIM provides uncompromised easy while, at the same time, offering applications towards...

Swarming is a collective bacterial behavior in which dense population of cells moves over porous surface, resulting the expansion population. This can guide bacteria away from potential stressors such as antibiotics and viruses. However, mechanisms responsible for organization swarms are not understood. Here, we briefly review models that based on sensing fluid mechanics proposed to swarming pathogenic bacterium

Significance Bacteria colonize surfaces and form dense biofilm communities in natural infection settings where flow is present. The physical mechanisms that give rise to the spatial organization of biofilms are not understood. Here, we show bacterium Pseudomonas aeruginosa uses a process have termed dynamic switching efficiently disperse throughout network maximize colonization. This dictates cells during transition from individual multicellular communities. Thus, establishes initial...

Pseudomonas aeruginosa is an opportunistic, multidrug-resistant, human pathogen that forms biofilms in environments with fluid flow, such as the lungs of cystic fibrosis patients, industrial pipelines, and medical devices. P. twitches upstream on surfaces by cyclic extension retraction its mechanoresponsive type IV pili motility appendages. The prevention motility, host invasion, infectious biofilm formation flow systems remains unmet challenge. Here, we describe design application scalable...