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We show that in a standardized in vitro flow system unencapsulated variants of genetically diverse lineages of Neisseria meningitidis formed biofilms, that could be maintained for more than 96 h. Biofilm cells were resistant to penicillin, but not to rifampin or ciprofloxacin. For some strains, microcolony formation within biofilms was observed. Microcolony formation in strain MC58 depended on a functional copy of the pilE gene encoding the pilus subunit pilin, and was associated with twitching of cells. Nevertheless, unpiliated pilE mutants formed biofilms showing that attachment and accumulation of cells did not depend on pilus expression. Mutation and complementation analysis revealed that the type IV pilus-associated protein PilX, which was recently shown to mediate interbacterial aggregation, indirectly supported microcolony formation by contributing to pilus expression. A large number of PilX alleles was identified among genetically diverse meningococcal strains. PilX alleles differed in their propensity to support autoaggregation of cells in suspension, but not in their ability to support microcolony formation within biofilms in the continuous flow system.
Mol Microbiol 2006 Dec
PMID:Meningococcal biofilm formation: structure, development and phenotypes in a standardized continuous flow system. 1712 95

Azoarcus sp. strain BH72, as an endophyte of grasses, depends on successful host colonization. Type IV pili are essential for mediating the initial interaction with rice roots. In the genome sequence analysis, the pilT gene was identified, which encodes for a putative type IV pilus retraction protein. PilT of Azoarcus sp. BH72 shares high similarity to PilT of the human pathogen Pseudomonas aeruginosa PAO1 (77% amino acid sequence identity) and contains a predicted nucleotide-binding motif. To gain more insights into the role of the type IV pili in the colonization process of Azoarcus spp., we constructed an insertional mutant of pilT and a deletion mutant of pilA, the major structural component of the pilus structure. The pilT mutant, as the pilin deletion mutant deltapilA, was abolished in twitching motility. Western blot analyses and electron microscopy studies demonstrated an enhanced piliation of the Azoarcus pilT mutant strain compared with the wild type, indicating that, indeed, PilT has a role in pilus retraction. Studies on rice root colonization in gnotobiotic cultures revealed that the establishment of microcolonies on the root surface was strongly reduced in the deltapilA mutant, whereas the surface colonization was reduced by only 50% in the nontwitching pilT mutant. However, endophytic colonization of rice roots was strongly reduced in both mutants. These results demonstrate that the retractile force mediated by PilT is not essential for the bacterial colonization of the plant surface, but that twitching motility is necessary for invasion of and establishment inside the plant. Thus, a novel determinant for endophytic interactions with grasses was identified.
Mol Plant Microbe Interact 2007 May
PMID:Twitching motility is essential for endophytic rice colonization by the N2-fixing endophyte Azoarcus sp. strain BH72. 1750 30

PKCalpha has been shown to be a negative regulator of contractility and PKCalpha gene deletion in mice protected against heart failure. Small interfering (si)RNAs mediate gene silencing by RNA interference (RNAi) and may be used to knockdown PKCalpha in cardiomyocytes. However, transfection efficiencies of (si)RNAs by lipofection tend to be low in primary cells. To address this limitation, we developed an adenoviral vector (AV) driving short hairpin (sh)RNAs against PKCalpha (Ad-shPKCalpha) and evaluated its potential to silence PKCalpha in neonatal rat cardiac myocytes and in engineered heart tissues (EHTs), which resemble functional myocardium in vitro. A nonsense encoding AV (Ad-shNS) served as control. Quantitative PCR and Western blotting showed 90% lower PKCalpha-mRNA and 50% lower PKCalpha protein in Ad-shPKCalpha-infected cells. EHTs were infected with Ad-shPKCalpha on day 11 and subjected to isometric force measurements in organ baths 4 days later. Mean twitch tension was >50% higher in Ad-shPKCalpha compared to Ad-shNS-infected EHTs, under basal and Ca(2+)- or isoprenaline-stimulated conditions. Twitch tension negatively correlated with PKCalpha mRNA levels. In summary, AV-delivered shRNA mediated highly efficient PKCalpha knockdown in cardiac myocytes and improved contractility in EHTs. The data support a role of PKCalpha as a negative regulator of myocardial contractility and demonstrate that EHTs in conjunction with AV-delivered shRNA are a useful model for target validation.
J Mol Cell Cardiol 2007 Sep
PMID:Adenovirus-delivered short hairpin RNA targeting PKCalpha improves contractile function in reconstituted heart tissue. 1762 88

Many bacterial species possess long filamentous structures known as pili or fimbriae extending from their surfaces. Despite the diversity in pilus structure and biogenesis, pili in Gram-negative bacteria are typically formed by non-covalent homopolymerization of major pilus subunit proteins (pilins), which generates the pilus shaft. Additional pilins may be added to the fiber and often function as host cell adhesins. Some pili are also involved in biofilm formation, phage transduction, DNA uptake and a special form of bacterial cell movement, known as 'twitching motility'. In contrast, the more recently discovered pili in Gram-positive bacteria are formed by covalent polymerization of pilin subunits in a process that requires a dedicated sortase enzyme. Minor pilins are added to the fiber and play a major role in host cell colonization.This review gives an overview of the structure, assembly and function of the best-characterized pili of both Gram-negative and Gram-positive bacteria.
Cell Mol Life Sci 2009 Feb
PMID:Pili in Gram-negative and Gram-positive bacteria - structure, assembly and their role in disease. 1895 86

Polymorphonuclear neutrophils are the most important mammalian host defence cells against infections with Pseudomonas aeruginosa. Screening of a signature tagged mutagenesis library of the non-piliated P. aeruginosa strain TBCF10839 uncovered that transposon inactivation of its pilY1 gene rendered the bacterium more resistant against killing by neutrophils than the wild type and any other of the more than 3000 tested mutants. Inactivation of pilY1 led to the loss of twitching motility in twitching-proficient wild-type PA14 and PAO1 strains, predisposed to autolysis and impaired the secretion of quinolones and pyocyanin, but on the other hand promoted growth in stationary phase and bacterial survival in murine airway infection models. The PilY1 population consisted of a major full-length and a minor shorter PilY1* isoform. PilY1* was detectable in small extracellular quinolone-positive aggregates, but not in the pilus. P. aeruginosa PilY1 is not an adhesin on the pilus tip, but assists in pilus biogenesis, twitching motility, secretion of secondary metabolites and in the control of cell density in the bacterial population.
Mol Microbiol 2009 Feb
PMID:Multiple roles of Pseudomonas aeruginosa TBCF10839 PilY1 in motility, transport and infection. 1905 30

Acidovorax avenae subsp. citrulli is the causal agent of bacterial fruit blotch (BFB), a threatening disease of watermelon, melon, and other cucurbits. Despite the economic importance of BFB, relatively little is known about basic aspects of the pathogen's biology and the molecular basis of its interaction with host plants. To identify A. avenae subsp. citrulli genes associated with pathogenicity, we generated a transposon (Tn5) mutant library on the background of strain M6, a group I strain of A. avenae subsp. citrulli, and screened it for reduced virulence by seed-transmission assays with melon. Here, we report the identification of a Tn5 mutant with reduced virulence that is impaired in pilM, which encodes a protein involved in assembly of type IV pili (TFP). Further characterization of this mutant revealed that A. avenae subsp. citrulli requires TFP for twitching motility and wild-type levels of biofilm formation. Significant reductions in virulence and biofilm formation as well as abolishment of twitching were also observed in insertional mutants affected in other TFP genes. We also provide the first evidence that group I strains of A. avenae subsp. citrulli can colonize and move through host xylem vessels.
Mol Plant Microbe Interact 2009 Aug
PMID:Type IV Pili are required for virulence, twitching motility, and biofilm formation of acidovorax avenae subsp. Citrulli. 1958 67

The aim of this study was to investigate the dynamics of lipid peroxidation and the possible correlation between lipid peroxidation in different brain regions and behavioral manifestations in lindane-induced seizures in rats. Male Wistar rats were divided into the following groups: 1. control, saline-treated group; 2. dimethylsulfoxide (DMSO)-treated group; 3. lindane-treated group (8 mg/kg), intraperitoneally. Animals were sacrificed 0.5 or 4 h after treatment and the malondialdehyde level and superoxide dismutase (SOD) activity were determined in various brain regions spectrophotometrically. Behavioral changes were classified according to the descriptive scale (0--no response, 1--head nodding, lower jaw twitching; 2--myoclonic body jerks, bilateral forelimb clonus with full rearing; 3--progression to generalized clonic convulsions followed by tonic extension of fore- and hind limbs and tail; 4--status epilepticus). A significant rise in the malondialdehyde level was detected in the cerebral cortex, hippocampus, and thalamus of lindane-treated animals 0.5 and 4 h after administration (P < 0.05). SOD activity (total and mitochondrial) was significantly decreased in the hippocampus and the cortex of lindane-treated animals at both time points (P < 0.05). An initial fall in SOD activity was detected in the thalamus 4 h after lindane administration (P < 0.05). A positive correlation between seizure severity and the malondialdehyde level was found in the hippocampus at both time points (P < 0.01). These results suggest that lipid peroxidation may contribute to the neurotoxic effects of lindane in early acute lindane intoxication and that behavioral manifestations correlate with lipid peroxidation in the hippocampus of lindane-treated rats.
Mol Cell Biochem 2010 Jan
PMID:The correlation between lipid peroxidation in different brain regions and the severity of lindane-induced seizures in rats. 1969 53

Microorganisms have various mechanisms at their disposal to react to (changes in) their ambient light climate (i.e., intensity, color, direction, and degree of polarization). Of these, one of the best studied mechanisms is the process of phototaxis. This process can be described as a behavioral migration-response of an organism toward a change in illumination regime. In this chapter we discuss three of these migration responses, based on swimming, swarming, and twitching motility, respectively. Swimming motility has been studied using a wide range of techniques, usually microscopy based. We present a detailed description of the assays used to study phototaxis in liquid cultures of the phototrophic organisms Halobacterium salinarum, Halorhodospira halophila, and Rhodobacter sphaeroides and briefly describe the molecular basis of these responses. Swarming and twitching motility are processes taking place at the interface between a solid phase and a liquid or gas phase. Although assays to study these processes are relatively straightforward, they are accompanied by technical complications, which we describe. Furthermore, we discuss the molecular processes underlying these forms of motility in Rhodocista centenaria and Synechocystis PCC6803. Recently, it has become clear that also chemotrophic organisms contain photoreceptor proteins that allow them to respond to their ambient light climate. Surprisingly, light-modulated motility responses can also be observed in the chemotrophic organisms Escherichia coli and Acinetobacter calcoaceticus. In the light-modulated surface migration not only "che-like" signal transduction reactions may play a role, but in addition processes as modulation of gene expression and even intermediary metabolism.
Methods Mol Biol 2009
PMID:Prokaryotic phototaxis. 1976 57

The highly conserved pilM/N/O/P/Q gene cluster is among the core set of genes required for cell surface expression of type IV pili and associated twitching motility. With the exception of the outer membrane secretin, a multimer of PilQ subunits, the specific functions of the products encoded by this gene cluster are poorly characterized. Orthologous proteins in the related bacterial type II secretion system have been shown to interact to form an inner membrane complex required for protein secretion. In this study, we provide evidence that the PilM/N/O/P proteins form a functionally equivalent type IVa pilus complex. Using Pseudomonas aeruginosa as model organism, we found that all four proteins, including the nominally cytoplasmic PilM, colocalized to the inner membrane. Stability studies via Western blot analyses revealed that loss of one component has a negative impact on the levels of other members of the putative complex. Furthermore, complementation studies revealed that the stoichiometry of the components is important for the correct formation of a stable complex in vivo. We provide evidence that an intact inner membrane complex is required for optimal formation of the outer membrane complex of the type IVa pilus system in P. aeruginosa, as PilQ stability is negatively affected in its absence. Finally, we show that, in the absence of the pilin subunit, the levels of membrane-bound components of the inner membrane complex are negatively regulated by the PilR/S two-component system, suggesting a role for PilR/S in sensing the piliation status of the cell.
J Mol Biol 2009 Nov 20
PMID:PilM/N/O/P proteins form an inner membrane complex that affects the stability of the Pseudomonas aeruginosa type IV pilus secretin. 1985 45

Type IV pili (T4P) are bacterial virulence factors responsible for attachment to surfaces and for twitching motility, a motion that involves a succession of pilus extension and retraction cycles. In the opportunistic pathogen Pseudomonas aeruginosa, the PilM/N/O/P proteins are essential for T4P biogenesis, and genetic and biochemical analyses strongly suggest that they form an inner-membrane complex. Here, we show through co-expression and biochemical analysis that the periplasmic domains of PilN and PilO interact to form a heterodimer. The structure of residues 69-201 of the periplasmic domain of PilO was determined to 2.2 A resolution and reveals the presence of a homodimer in the asymmetric unit. Each monomer consists of two N-terminal coiled coils and a C-terminal ferredoxin-like domain. This structure was used to generate homology models of PilN and the PilN/O heterodimer. Our structural analysis suggests that in vivo PilN/O heterodimerization would require changes in the orientation of the first N-terminal coiled coil, which leads to two alternative models for the role of the transmembrane domains in the PilN/O interaction. Analysis of PilN/O orthologues in the type II secretion system EpsL/M revealed significant similarities in their secondary structures and the tertiary structures of PilO and EpsM, although the way these proteins interact to form inner-membrane complexes appears to be different in T4P and type II secretion. Our analysis suggests that PilN interacts directly, via its N-terminal tail, with the cytoplasmic protein PilM. This work shows a direct interaction between the periplasmic domains of PilN and PilO, with PilO playing a key role in the proper folding of PilN. Our results suggest that PilN/O heterodimers form the foundation of the inner-membrane PilM/N/O/P complex, which is critical for the assembly of a functional T4P complex.
J Mol Biol 2009 Nov 20
PMID:Periplasmic domains of Pseudomonas aeruginosa PilN and PilO form a stable heterodimeric complex. 1985 46


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