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PubMed1987

Anomalous uncoupling of photophosphorylation by palmitic acid and by gramicidin D.

Palmitic acid and gramicidin D at low concentrations uncouple photophosphorylation in a mechanism that is inconsistent with classical uncoupling in the following properties: (1) delta pH, H+ uptake, or the transmembrane electric potential is not inhibited. (2) O2 evolution is stimulated under nonphosphorylating conditions but slightly inhibited in the presence of adenosine 5'-diphosphate + inorganic phosphate (Pi). (3) Light-triggered adenosine 5'-triphosphate (ATP)-Pi exchange is hardly affected, and ATPase activity is only slightly stimulated. (4) ATP-induced delta pH formation is selectively inhibited. This characteristic uncoupling is observed only when the native coupling sites of the electron transport system are used for energization such as for methylviologen-coupled phosphorylation. With pyocyanine, which creates an artificial coupling site, 1000-fold higher gramicidin D and higher palmitic acid concentrations are required for inhibition, and the inhibition is accompanied by a decrease in delta pH. Moreover, comparison between photosystem 1 and photosystem 2 electron transport and the effects of membrane unstacking suggest that low gramicidin D preferentially inhibits photosystem 2, while palmitic acid inhibits more effectively photosystem 1 coupling sites. The inhibitory capacity of fatty acids significantly drops when the chain length is reduced below 16 hydrocarbons or upon introduction of a single double bond in the hydrocarbon chain. It is suggested that palmitic acid and gramicidin D interfere with a direct H+ transfer between specific electron transport and the ATP synthase complexes, which provides an alternative coupling mechanism in parallel with bulk to bulk delta microH+. The sites of inhibition seem to be located in chloroplast ATP synthase, photosystem 2, and the cytochrome b6f complexes.

Chloroplasts↗

PubMed2004

Structure and function of the phenazine biosynthesis protein PhzF from Pseudomonas fluorescens 2-79.

Phenazines, including pyocyanin and iodonin, are biologically active compounds that are believed to confer producing organisms with a competitive growth advantage, and also are thought to be virulence factors in certain diseases including cystic fibrosis. The basic, tricyclic phenazine ring system is synthesized in a series of poorly characterized steps by enzymes encoded in a seven-gene cistron in Pseudomonas and other organisms. Despite the biological importance of these compounds, and our understanding of their mode of action, the biochemistry and mechanisms of phenazine biosynthesis are not well resolved. Here we report the 1.8 A crystal structure of PhzF, a key enzyme in phenazine biosynthesis, solved by molecular replacement. PhzF is structurally similar to the lysine biosynthetic enzyme diaminopimelate epimerase, sharing an unusual fold consisting of two nearly identical domains with the active site located in an occluded cleft between the domains. Unlike diaminopimelate epimerase, PhzF is a dimer in solution. The two apparently independent active sites open toward opposite sides of the dimer and are occupied by sulfate ions in the structure. In vitro experiments using a mixture of purified PhzF, -A, -B, and -G confirm that phenazine-1-carboxylic acid (PCA) is readily produced from trans-2,3-dihydro-3-hydroxyanthranilic acid (DHHA) without aid of other cellular factors. PhzA, -B, and -G have no activity toward DHHA. However, in the presence of PhzF, individually or in combinations, they accelerate the formation of PCA from DHHA and therefore appear to function after the action of PhzF. Surprisingly, PhzF is itself capable of producing PCA, albeit slowly, from DHHA. These observations suggest that PhzF catalyzes the initial step in the conversion of DHHA to PCA, probably via a rearrangement reaction yielding the more reactive 3-oxo analogue of DHHA, and that subsequent steps can occur spontaneously. A hypothetical model for how DHHA binds to the PhzF active site suggests that Glu45 and Asp208 could act as general acid-base catalysts in a rearrangement reaction. Given that four reactions lie between DHHA and PCA, ketone formation, ring formation, decarboxylation, and oxidation, we hypothesize that the similar PhzA and -B proteins catalyze ring formation and thus may be more than noncatalytic accessory proteins. PhzG is almost certainly an oxidase and is predicted to catalyze the final oxidation/aromatization reaction.

3-Hydroxyanthranilic Acid↗

PubMed1997

Characterization of MexE-MexF-OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa.

Antibiotic-resistant mutants of Pseudomonas aeruginosa were generated using chloramphenicol and ciprofloxacin as selective agents. These mutants displayed a multidrug phenotype and overexpressed an outer membrane protein of 50 kDa, which was shown by Western blot analysis to correspond to OprN. A cosmid clone harbouring the oprN gene was isolated by partial complementation of a mutant deficient in OprM, the outer membrane component of the mexAB-oprM efflux operon. Antibiotic-accumulation studies indicated that OprN was part of an energy-dependent antibiotic-efflux system. Sequencing of a 6180bp fragment from the complementing cosmid revealed the presence of three open reading frames (ORFs), which exhibited amino acid similarity to the components of the mexAB-oprM and mexCD-oprJ efflux operons of P. aeruginosa. The ORFs were designated MexE, MexF and OprN. Mutation of the mexE gene eliminated the multidrug-resistance phenotype in an OprN-overexpressing strain, but did not affect the susceptibility profile of the wild-type strain. Expression of the mexEF-oprN operon was shown to be positively regulated by a protein encoded on a 1.5 kb DNA fragment located upstream of mexE and belonging to the LysR family of transcriptional activators. The presence of a plasmid containing this DNA fragment was sufficient to confer a multidrug phenotype onto the wild-type strain but not onto the mexE mutant. Evidence is provided to show that the mexEF-oprN operon may be involved in the excretion of intermediates for the biosynthesis of pyocyanin, a typical secondary metabolite of P. aeruginosa.

Amino Acid Sequence↗

PubMed2003

Acyl-homoserine lactone acylase from Ralstonia strain XJ12B represents a novel and potent class of quorum-quenching enzymes.

N-acylhomoserine lactones (AHLs) are used as signal molecules by many quorum-sensing Proteobacteria. Diverse plant and animal pathogens use AHLs to regulate infection and virulence functions. These signals are subject to biological inactivation by AHL-lactonases and AHL-acylases. Previously, little was known about the molecular details underlying the latter mechanism. An AHL signal-inactivating bacterium, identified as a Ralstonia sp., was isolated from a mixed-species biofilm. The signal inactivation encoding gene from this organism, which we call aiiD, was cloned and successfully expressed in Escherichia coli and inactivated three AHLs tested. The predicted 794-amino-acid polypeptide was most similar to the aculeacin A acylase (AAC) from Actinoplanes utahensis and also shared significant similarities with cephalosporin acylases and other N-terminal (Ntn) hydrolases. However, the most similar homologues of AiiD are deduced proteins of undemonstrated function from available Ralstonia, Deinococcus and Pseudomonas genomes. LC-MS analyses demonstrated that AiiD hydrolyses the AHL amide, releasing homoserine lactone and the corresponding fatty acid. Expression of AiiD in Pseudomonas aeruginosa PAO1 quenched quorum sensing by this bacterium, decreasing its ability to swarm, produce elastase and pyocyanin and to paralyze nematodes. Thus, AHL-acylases have fundamental implications and hold biotechnological promise in quenching quorum sensing.

4-Butyrolactone↗

PubMed2004

Structure and function of the phenazine biosynthetic protein PhzF from Pseudomonas fluorescens.

Phenazines produced by Pseudomonas and Streptomyces spp. are heterocyclic nitrogen-containing metabolites with antibiotic, antitumor, and antiparasitic activity. The antibiotic properties of pyocyanin, produced by Pseudomonas aeruginosa, were recognized in the 1890s, although this blue phenazine is now known to be a virulence factor in human disease. Despite their biological significance, the biosynthesis of phenazines is not fully understood. Here we present structural and functional studies of PhzF, an enzyme essential for phenazine synthesis in Pseudomonas spp. PhzF shares topology with diaminopimelate epimerase DapF but lacks the same catalytic residues. The structure of PhzF in complex with its substrate, trans-2,3-dihydro-3-hydroxyanthranilic acid, suggests that it is an isomerase using the conserved glutamate E45 to abstract a proton from C3 of the substrate. The proton is returned to C1 of the substrate after rearrangement of the double-bond system, yielding an enol that converts to the corresponding ketone. PhzF is a dimer that may be bifunctional, providing a shielded cavity for ketone dimerization via double Schiff-base formation to produce the phenazine scaffold. Our proposed mechanism is supported by mass and NMR spectroscopy. The results are discussed in the context of related structures and protein sequences of unknown biochemical function.

Bacterial Proteins↗

PubMed2005

The power of chemical genomics to study the link between endomembrane system components and the gravitropic response.

Chemical genomics is a powerful approach to dissect processes that may be intractable using conventional genetics because of gene lethality or redundancy. Recently, a link has been established between endomembrane trafficking and gravitropism. To understand this link, we screened a library of 10,000 diverse chemicals for compounds that affected the gravitropism of Arabidopsis seedlings positively or negatively. Sixty-nine of 219 compounds from the primary screen were retested, and 34 of these were confirmed to inhibit or enhance gravitropism. Four of the 34 compounds were found to cause aberrant endomembrane morphologies. The chemicals affected gravitropism and vacuole morphology in concert in a tissue-specific manner, underscoring the link between endomembranes and gravitropism. One of the chemicals (5403629) was structurally similar to the synthetic auxin 2,4-dichlorophenoxy acetate, whereas the other three chemicals were unique in their structures. An in vivo functional assay using the reporter beta-glucuronidase under the auxin-inducible DR5 promoter confirmed that the unique compounds were not auxins. Interestingly, one of the unique chemicals (5850247) appeared to decrease the responsiveness to auxin in roots, whereas another (5271050) was similar to pyocyanin, a bacterial metabolite that has been suggested to target the endomembranes of yeast. These reagents will be valuable for dissecting endomembrane trafficking and gravitropism and for cognate target identification.

Arabidopsis↗

PubMed1971

Interactions between ADP and the coupling factor of photophosphorylation.

The coupling factor of photophosphorylation, which carries out the terminal steps in the light-dependent synthesis of ATP in spinach chloroplasts, forms tight complexes with [(14)C]ADP in vitro. The bound [(14)C]ADP undergoes a transphosphorylation reaction to give [(14)C]AMP and [(14)C]ATP. The [(14)C]ATP remains tightly bound, and can be recovered conveniently only by denaturation of the enzyme nucleotide complex. If spinach membranes are illuminated in the presence of pyocyanine and [(3)H]AMP or [(32)P]P(i), the enzyme can be recovered as a tight complex with [(3)H]ADP or [(32)P]ADP. The evidence indicates that AMP is an earlier acceptor of phosphate than is ADP, in a light-driven phosphorylation reaction. It also suggests that AMP serves as a cofactor in photophosphorylation.

Adenine Nucleotides↗

PubMed1992

Nitric oxide synthase in macula densa regulates glomerular capillary pressure.

Tubular-fluid reabsorption by specialized cells of the nephron at the junction of the ascending limb of the loop of Henle and the distal convoluted tubule, termed the macula densa, releases compounds causing vasoconstriction of the adjacent afferent arteriole. Activation of this tubuloglomerular feedback response reduces glomerular capillary pressure of the nephron and, hence, the glomerular filtration rate. The tubuloglomerular feedback response functions in a negative-feedback mode to relate glomerular capillary pressure to tubular-fluid delivery and reabsorption. This system has been implicated in renal autoregulation, renin release, and longterm body fluid and blood-pressure homeostasis. Here we report that arginine-derived nitric oxide, generated in the macula densa, is an additional intercellular signaling molecule that is released during tubular-fluid reabsorption and counters the vasoconstriction of the afferent arteriole. Antibody to rat cerebellar constitutive nitric oxide synthase stained rat macula densa cells specifically. Microperfusion of the macula densa segment of single nephrons with N omega-methyl-L-arginine (an inhibitor of nitric oxide synthase) or with pyocyanin (a lipid-soluble inhibitor of endothelium-derived relaxation factor) showed that generation of nitric oxide can vasodilate the afferent arteriole and increase glomerular capillary pressure; this effect was blocked by drugs that prevent tubular-fluid reabsorption. We conclude that nitric oxide synthase in macula densa cells is activated by tubular-fluid reabsorption and mediates a vasodilating component to the tubuloglomerular feedback response. These findings imply a role for arginine-derived nitric oxide in body fluid-volume and blood-pressure homeostasis, in addition to its established roles in modulation of vascular tone by the endothelium and in neurotransmission.

Amino Acid Oxidoreductases↗

PubMed1999

Pseudomonas libanensis sp. nov., a new species isolated from Lebanese spring waters.

The taxonomic position of eight fluorescent Pseudomonas isolates, from two Lebanese spring waters, which were previously recognized by numerical analysis as members of a new subcluster (subcluster Vb) was examined. Except for one strain, the new subcluster exhibited internal DNA hybridization values of 76-100%, and 9-53% hybridization was measured with the type or reference strains of other Pseudomonas species. The highest DNA binding value was found with Pseudomonas marginalis strains (37-53%). The G+C content of the DNA of the type strain was 58 mol%. A comparison of 1322 nt of the 16S rRNA gene sequence of the strain representing subcluster Vb (CFML 96-195T) with the sequence of other strains of the genus Pseudomonas revealed that strain CFML 96-195T was part of the 'Pseudomonas fluorescens intrageneric cluster'. On the basis of the results of phenotypic, DNA-DNA and phylogenetic analyses, a new Pseudomonas species, Pseudomonas libanensis sp. nov., is proposed for the seven strains of subcluster Vb. The type strain is P. libanensis CFML 96-195T and has been deposited in the Collection de l'Institut Pasteur (Paris, France) as CIP 105460T. The P. libanensis strains are phenotypically and genotypically homogeneous and can be differentiated from most other fluorescent species by several phenotypic features. Differentiation of P. libanensis and Pseudomonas aeruginosa is based mainly on pyocyanin production; P. libanensis can be differentiated from P. fluorescens (all biovars) by alpha-aminobutyrate assimilation. The clinical significance of P. libanensis is unknown.

Bacterial Typing Techniques↗

PubMed2002

Genetically programmed autoinducer destruction reduces virulence gene expression and swarming motility in Pseudomonas aeruginosa PAO1.

Virulence in the opportunistic human pathogen Pseudomonas aeruginosa is controlled by cell density via diffusible signalling molecules ('autoinducers') of the N-acylhomoserine lactone (AHL) type. Two Bacillus sp. isolates (A23 and A24) with AHL-degrading activity were identified among a large collection of rhizosphere bacteria. From isolate A24 a gene was cloned which was similar to the aiiA gene, encoding an AHL lactonase in another Bacillus strain. Expression of the aiiA homologue from isolate A24 in P. aeruginosa PAO1 reduced the amount of the quorum sensing signal N-oxododecanoyl-L-homoserine lactone and completely prevented the accumulation of the second AHL signal, N-butyryl-L-homoserine lactone. This strongly reduced AHL content correlated with a markedly decreased expression and production of several virulence factors and cytotoxic compounds such as elastase, rhamnolipids, hydrogen cyanide and pyocyanin, and strongly reduced swarming. However, no effect was observed on flagellar swimming or on twitching motility, and aiiA expression did not affect bacterial adhesion to a polyvinylchloride surface. In conclusion, introduction of an AHL degradation gene into P. aeruginosa could block cell-cell communication and exoproduct formation, but failed to interfere with surface colonization.

Bacillus↗

PubMed2002

Characterization of a new efflux pump, MexGHI-OpmD, from Pseudomonas aeruginosa that confers resistance to vanadium.

Vanadium has an antibacterial activity against Pseudomonas aeruginosa, especially under conditions of iron limitation. Some degree of resistance to V is inducible by prior exposure to the metal. One mutant (VS1) with a higher sensitivity to V was obtained by transposon mutagenesis of P. aeruginosa PA 59.20, a clinical isolate. This mutant had an insertion in a non-coding region, upstream of a cluster of four genes. Three of them show similarities to genes corresponding to known P. aeruginosa antibiotic efflux systems, including an efflux protein, a membrane fusion protein and an outer-membrane porin. This cluster was named mexGHI-opmD. By allelic exchange, three mutants, ncr (for non-coding region), mexI and opmD were constructed in P. aeruginosa PAO1. Next to V sensitivity, the ncr, mexI and opmD mutants also showed reduced production of elastase, rhamnolipids, pyocyanine, pyoverdine and had reduced swarming motility, phenotypes that are known to be regulated by quorum sensing. All wild-type phenotypes, including growth in the presence of V, were restored by complementation with the complete cluster. The production of N-acyl-homoserine lactones (AHLs) was detected using the Chromobacter violaceum bioassay. Total extracts from the three mutants failed to induce the production of violacein by C. violaceum, although AHLs were detected by TLC and C. violaceum overlay. Violacein production was restored by complementation with mexGHI-opmD. The opmD mutant grew very slowly in LB or CAA medium, indicating that OpmD has an important physiological function for the cell. In conclusion, it is believed that the MexGHI-OpmD pump is probably involved in AHL homeostasis in P. aeruginosa.

Base Sequence↗

PubMed1979

Differentiation of fluorescent pseudomonads by their effect on milk agar.

Eighty-six clinical isolates of fluorescent pseudomonads that did not produce pyocyanin on Diagnostic Sensitivity Test Agar or Cetrimide Agar were identified on the basis of their antibiotic sensitivity, production of pigment on King's "A" medium, growth at 42 degrees C, production of lecithinase and hydrolysis of gelatin. The identity of the strains was confirmed in tests with the ammonium salt sugars ethanol, glucose and mannitol. These tests were adequate for distinguishing between the three important fluorescent pseudomonads. The detection of casein hydrolysis on milk agar was assessed as a rapid method of distinguishing P. aeruginosa from the other species of fluorescent pseudomonads but proved unhelpful when compared with, or included in, a small set of tests. Most strains of P. aeruginosa and P. fluorescens hydrolysed casein.

Agar↗

PubMed1991

Interaction between Pseudomonas aeruginosa and Staphylococcus aureus: description of an anti-staphylococcal substance.

The presence of Pseudomonas aeruginosa in the sputum of 191 patients with cystic fibrosis was significantly related (p less than 0.0001) to the absence of Staphylococcus aureus. Cross-streaking tests showed that 40 of 50 clinical strains of P. aeruginosa produced substances that inhibited the growth of S. aureus. When incorporated into agar plates, this antibacterial substance(s) inhibited the growth of 177 of 189 strains of nine staphylococcal species, all of 16 methicillin-resistant S. aureus and 27 of 39 strains of six other gram-positive genera. The substance(s) did not inhibit 23 strains of seven gram-negative genera tested. The antibacterial activity was heat stable and could be extracted into chloroform; activity was retained on Sephadex G-15 (V/Vo approximately 2, Mr less than 500) and eluted as a single peak from high performance liquid chromatography, well separated from pseudomonic acid, pyocyanin and a number of other phenazines.

Anti-Bacterial Agents↗

PubMed1975

Inhibition of Cryptococcus neoformans by Pseudomonas aeruginosa.

Pseudomonas aeruginosa was found to produce a factor or factors that inhibited Cryptococcus neoformans and appeared to be extracellular because the anti-C. neoformans activity was readily demonstrable in medium after the removal and killing of Pseudomonas organisms. Production of the inhibitor material was greatest in DST Agar after prolonged incubation and was reduced in the presence of glucose. A part of the inhibitory material was found to be chromatographically distinct from pyocyanin.

Antibiosis↗

PubMed2004

Analysis of quorum sensing-deficient clinical isolates of Pseudomonas aeruginosa.

Pseudomonas aeruginosa produces multiple virulence factors and causes different types of infections. Previous clinical studies identified P. aeruginosa isolates that lack individual virulence factors. However, the impact of losing several virulence factors simultaneously on the in vivo virulence of P. aeruginosa is not completely understood. The P. aeruginosa cell-to-cell communication system, or quorum sensing (QS), controls the production of several virulence factors. Animal studies using constructed QS mutants indicated that loss of the QS system severely impacts the virulence of P. aeruginosa. In this study, we tried to determine if deficiency within the QS system compromises the ability of P. aeruginosa to establish infections in humans. We have identified five QS-deficient strains through screening 200 isolates from patients with urinary tract, lower respiratory tract and wound infections. These strains lacked LasB and LasA activities and produced either no or very low levels of the autoinducers N-(3-oxododecanoyl) homoserine lactone and N-butyryl homoserine lactone. PCR analysis revealed that three isolates contained all four QS genes (lasI, lasR, rhlI and rhlR) while two isolates lacked both the lasR and rhlR genes. We also examined the five isolates for other virulence factors. The isolates produced variable levels of exotoxin A and, with one exception, were deficient in pyocyanin production. One isolate produced the type III secretion system (TTSS) effector proteins ExoS and ExoT, two isolates produced ExoT only and two isolates produced no TTSS proteins. The isolates produced weak to moderate biofilms on abiotic surfaces. Analysis of the patients' data revealed that two of the isolates represented a single strain that was isolated twice from the same patient within a 1 month interval. One QS-deficient clinical isolate (CI-1) lacked all tested virulence factors and produced a weak biofilm. These results suggest that naturally occurring QS-deficient strains of P. aeruginosa do occur and are capable of causing infections; and, that besides the known virulence factors, additional factors may contribute to the ability of certain strains such as CI-1 to establish an infection.

4-Butyrolactone↗

PubMed2004

Emergence of phenotypic variants upon mismatch repair disruption in Pseudomonas aeruginosa.

MutS is part of the bacterial mismatch repair system that corrects point mutations and small insertions/deletions that fail to be proof-read by DNA polymerase activity. In this work it is shown that the disruption of the P. aeruginosa mutS gene generates the emergence of diverse colony morphologies in contrast with its parental wild-type strain that displayed monomorphic colonies. Interestingly, two of the mutS morphotypes emerged at a high frequency and in a reproducible way and were selected for subsequent characterization. One of them displayed a nearly wild-type morphology while the other notably showed, compared with the wild-type strain, increased production of pyocyanin and pyoverdin, lower excretion of LasB protease and novel motility characteristics, mainly related to swarming. Furthermore, it was reproducibly observed that, after prolonged incubation in liquid culture, the pigmented variant consistently emerged from the mutS wild-type-like variant displaying a reproducible event. It is also shown that these P. aeruginosa mutS morphotypes not only displayed an increase in the frequency of antibiotic-resistant mutants, as described for clinical P. aeruginosa mutator isolates, but also generated mutants whose antibiotic-resistant levels were higher than those measured from spontaneous resistant mutants derived from wild-type cells. It was also found that both morphotypes showed a decreased cytotoxic capacity compared to the wild-type strain, leading to the emergence of invasive variants. By using mutated versions of a tetracycline resistance gene, the mutS mutant showed a 70-fold increase in the reversion frequency of a +1 frameshift mutation with respect to its parental wild-type strain, allowing the suggestion that the phenotypical diversity generated in the mutS population could be produced in part by frameshift mutations. Finally, since morphotypical diversification has also been described in clinical isolates, the possibility that this mutS diversification was related to the high frequency hypermutability observed in P. aeruginosa CF isolates is discussed.

Adenosine Triphosphatases↗

PubMed2025

Pseudomonas aeruginosa phenazines dictate site-specific competitive interactions with Klebsiella pneumoniae.

Pseudomonas aeruginosa and Klebsiella pneumoniae are Gram-negative opportunistic pathogens that frequently colonize the human body and are major causes of infection. These bacteria are often co-isolated in polymicrobial urinary tract and lung infections, the latter of which is associated with increased disease severity and worse clinical outcomes. Despite their overlapping niches and clinical relevance, little is known about how these two pathogens interact and how those interactions influence human health. Given the growing recognition that microbial interactions are key drivers of disease, we investigated how P. aeruginosa and K. pneumoniae influence one another. We discovered an antagonistic interaction in which P. aeruginosa restricts the growth of K. pneumoniae. This inhibition is driven by phenazine production in P. aeruginosa, specifically the secondary metabolites pyocyanin and pyorubin, which are both necessary and sufficient to suppress K. pneumoniae growth. Using a diverse set of clinical isolates, we found that this antagonism is strain dependent. Both the susceptibility of K. pneumoniae to phenazines and the ability of P. aeruginosa to restrict K. pneumoniae growth varies between strains. Moreover, the necessity of phenazine production is specific to the site of infection. Together, these findings demonstrate that strain background and environmental context are critical determinants of pathogen interactions. Our work underscores the importance of considering these variables when investigating how microbial interactions influence infection and disease outcomes.

Journal Article↗

PubMed2025

Mapping genetic and phenotypic diversity of Pseudomonas aeruginosa across clinical and environmental isolation sites.

Pseudomonas aeruginosa is a clinically significant opportunistic pathogen adept at thriving in both host-associated and environmental settings. To define the extent to which P. aeruginosa isolates specialize across niches and identify genotype-phenotype correlates, we performed whole genome sequencing and comprehensive phenotypic characterization of 125 P. aeruginosa isolates from diverse clinical and environmental sites, evaluating virulence-associated traits, including motility, cytotoxicity, biofilm formation, pyocyanin production, and antimicrobial susceptibility. We identify that genomic diversity does not correlate with isolation source or most virulence phenotypes. Instead, we find that the two major P. aeruginosa clades (Groups A and B) delineate phylogeny and cytotoxicity, with Group B strains showing significantly higher cytotoxicity than Group A. Sequence analysis revealed previously uncharacterized alleles of genes encoding type III secretion effector proteins. We observed high variability amongst strains and isolation sources in all four assayed virulence phenotypes. Antimicrobial resistance (AMR) is exclusively observed in clinical isolates, not environmental, reflecting antibiotic exposure-driven selection. Bacterial GWAS revealed a statistically significant association between cytotoxicity and exoU presence, and we identified a novel exoU allelic variant with decreased cytotoxicity, demonstrating that functional diversity within well-characterized virulence factors may still influence pathogenic outcomes. In summary, our analyses of 125 diverse isolates suggest that the ability of P. aeruginosa to thrive across diverse niches is driven by broadly conserved genetic repertoire rather than niche-specific accessory genes.

Journal Article↗