scholarly journals Molecular Mechanisms of Staphylococcus and Pseudomonas Interactions in Cystic Fibrosis

2022 ◽  
Vol 11 ◽  
Author(s):  
Lalitha Biswas ◽  
Friedrich Götz
Keyword(s):  
Cystic Fibrosis ◽  
Molecular Mechanisms ◽  
Genetic Disorder ◽  
Protein A ◽  
Chronic Infections ◽  
Transport Pathway ◽  
Small Colony Variant ◽  
Cooperative Interactions ◽  
Small Colony ◽  
Infancy And Early Childhood

Cystic fibrosis (CF) is an autosomal recessive genetic disorder that is characterized by recurrent and chronic infections of the lung predominantly by the opportunistic pathogens, Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. While S. aureus is the main colonizing bacteria of the CF lungs during infancy and early childhood, its incidence declines thereafter and infections by P. aeruginosa become more prominent with increasing age. The competitive and cooperative interactions exhibited by these two pathogens influence their survival, antibiotic susceptibility, persistence and, consequently the disease progression. For instance, P. aeruginosa secretes small respiratory inhibitors like hydrogen cyanide, pyocyanin and quinoline N-oxides that block the electron transport pathway and suppress the growth of S. aureus. However, S. aureus survives this respiratory attack by adapting to respiration-defective small colony variant (SCV) phenotype. SCVs cause persistent and recurrent infections and are also resistant to antibiotics, especially aminoglycosides, antifolate antibiotics, and to host antimicrobial peptides such as LL-37, human β-defensin (HBD) 2 and HBD3; and lactoferricin B. The interaction between P. aeruginosa and S. aureus is multifaceted. In mucoid P. aeruginosa strains, siderophores and rhamnolipids are downregulated thus enhancing the survival of S. aureus. Conversely, protein A from S. aureus inhibits P. aeruginosa biofilm formation while protecting both P. aeruginosa and S. aureus from phagocytosis by neutrophils. This review attempts to summarize the current understanding of the molecular mechanisms that drive the competitive and cooperative interactions between S. aureus and P. aeruginosa in the CF lungs that could influence the disease outcome.

scholarly journals Single-molecule visualization of human BLM helicase as it acts upon double- and single-stranded DNA substrates

2019 ◽  
Vol 47 (21) ◽  
pp. 11225-11237 ◽  
Author(s):  
Chaoyou Xue ◽  
James M Daley ◽  
Xiaoyu Xue ◽  
Justin Steinfeld ◽  
Youngho Kwon ◽  
...  
Keyword(s):  
Single Molecule ◽  
Molecular Mechanisms ◽  
Genetic Disorder ◽  
Protein A ◽  
Base Pairs ◽  
Single Stranded Dna ◽  
Double Stranded Dna ◽  
Blm Helicase ◽  
Dna Replication And Repair ◽  
Regulatory Effects

Abstract Bloom helicase (BLM) and its orthologs are essential for the maintenance of genome integrity. BLM defects represent the underlying cause of Bloom Syndrome, a rare genetic disorder that is marked by strong cancer predisposition. BLM deficient cells accumulate extensive chromosomal aberrations stemming from dysfunctions in homologous recombination (HR). BLM participates in several HR stages and helps dismantle potentially harmful HR intermediates. However, much remains to be learned about the molecular mechanisms of these BLM-mediated regulatory effects. Here, we use DNA curtains to directly visualize the activity of BLM helicase on single molecules of DNA. Our data show that BLM is a robust helicase capable of rapidly (∼70–80 base pairs per second) unwinding extensive tracts (∼8–10 kilobases) of double-stranded DNA (dsDNA). Importantly, we find no evidence for BLM activity on single-stranded DNA (ssDNA) that is bound by replication protein A (RPA). Likewise, our results show that BLM can neither associate with nor translocate on ssDNA that is bound by the recombinase protein RAD51. Moreover, our data reveal that the presence of RAD51 also blocks BLM translocation on dsDNA substrates. We discuss our findings within the context of potential regulator roles for BLM helicase during DNA replication and repair.

Thymidine‐auxotrophic Staphylococcus aureus small‐colony variant bacteremia in a patient with cystic fibrosis

2020 ◽  
Vol 55 (6) ◽  
pp. 1388-1393
Author(s):  
Dilair C. Souza ◽  
Laura L. Cogo ◽  
Jussara K. Palmeiro ◽  
Libera M. Dalla‐Costa ◽  
Ana P. Oliveira Tomaz ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Small Colony Variant ◽  
Small Colony

scholarly journals Anex vivocystic fibrosis model recapitulates key clinical aspects of chronicStaphylococcus aureusinfection

2019 ◽  
Author(s):  
Esther Sweeney ◽  
Marwa M. Hassan ◽  
Niamh E. Harrington ◽  
Alan R. Smyth ◽  
Matthew N. Hurley ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Ex Vivo ◽  
Lung Model ◽  
Clinical Aspects ◽  
Small Colony Variant ◽  
Tissue Invasion ◽  
Disease Characteristics ◽  
Small Colony ◽  
Clinically Significant

AbstractStaphylococcus aureusis one of the most prevalent organisms isolated from the airways of people with cystic fibrosis (CF), predominantly early in life. Yet its role in the pathology of lung disease is poorly understood. Clinical studies are limited in scope by age and health of participants andin vitrostudies are not always able to accurately recapitulate chronic disease characteristics such as the development of small colony variants. Further, animal models also do not fully represent features of clinical disease: in particular, mice are not readily colonized byS. aureusand when infection is established it leads to the formation of abscesses, a phenomenon almost never observed in the human CF lung. Here, we present details of the development of an existingex vivopig lung model of CF infection to investigate the growth ofS. aureus. We show thatS. aureusis able to establish infection and demonstrates clinically significant characteristics including small colony variant phenotype, increased antibiotic tolerance and preferential localisation in mucus. Tissue invasion and the formation of abscesses were not observed, in line with clinical data.

Interference ofPseudomonas aeruginosasignalling and biofilm formation for infection control

2010 ◽  
Vol 12 ◽  
Author(s):  
Thomas Bjarnsholt ◽  
Tim Tolker-Nielsen ◽  
Niels Høiby ◽  
Michael Givskov
Keyword(s):  
Cystic Fibrosis ◽  
Biofilm Formation ◽  
Molecular Mechanisms ◽  
Antibiotic Tolerance ◽  
Chronic Infections ◽  
Major Task ◽  
Vitro Data ◽  
In Vitro Data

Pseudomonas aeruginosais the best described bacterium with regards to quorum sensing (QS), in vitro biofilm formation and the development of antibiotic tolerance. Biofilms composed ofP. aeruginosaare thought to be the underlying cause of many chronic infections, including those in wounds and in the lungs of patients with cystic fibrosis. In this review, we provide an overview of the molecular mechanisms involved in QS, QS-enabled virulence, biofilm formation and biofilm-enabled antibiotic tolerance. We now have substantial knowledge of the multicellular behaviour ofP. aeruginosain vitro. A major task for the future is to investigate how such in vitro data correlate with the in vivo behaviour ofP. aeruginosa, and how to treat chronic infections of this bacterium in patients.

scholarly journals Expression Analysis of a Highly Adherent and Cytotoxic Small Colony Variant of Pseudomonas aeruginosa Isolated from a Lung of a Patient with Cystic Fibrosis

2004 ◽  
Vol 186 (12) ◽  
pp. 3837-3847 ◽  
Author(s):  
Franz von Götz ◽  
Susanne Häussler ◽  
Doris Jordan ◽  
Senthil Selvan Saravanamuthu ◽  
Dirk Wehmhöner ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Dna Microarrays ◽  
Effector Proteins ◽  
Wild Type ◽  
Small Colony Variant ◽  
A Genome ◽  
Small Colony ◽  
Type Iii Protein Secretion

ABSTRACT The heterogeneous environment of the lung of the cystic fibrosis (CF) patient gives rise to Pseudomonas aeruginosa small colony variants (SCVs) with increased antibiotic resistance, autoaggregative growth behavior, and an enhanced ability to form biofilms. In this study, oligonucleotide DNA microarrays were used to perform a genome-wide expression study of autoaggregative and highly adherent P. aeruginosa SCV 20265 isolated from a CF patient's lung in comparison with its clonal wild type and a revertant generated in vitro from the SCV population. Most strikingly, SCV 20265 showed a pronounced upregulation of the type III protein secretion system (TTSS) and the respective effector proteins. This differential expression was shown to be biologically meaningful, as SCV 20265 and other hyperpiliated and autoaggregative SCVs with increased TTSS expression were significantly more cytotoxic for macrophages in vitro and were more virulent in a mouse model of respiratory tract infection than the wild type. The observed cytotoxicity and virulence of SCV 20265 required exsA, an important transcriptional activator of the TTSS. Thus, the prevailing assumption that P. aeruginosa is subject to selection towards reduced cytotoxicity and attenuated virulence during chronic CF lung infection might not apply to all clonal variants.

scholarly journals Lack of Association of Small-Colony-Variant Staphylococcus aureus Strains with Long-Term Use of Azithromycin in Patients with Cystic Fibrosis : Table 1.

2011 ◽  
Vol 49 (7) ◽  
pp. 2772-2773 ◽  
Author(s):  
Nicole Green ◽  
Jane L. Burns ◽  
Nicole Mayer-Hamblett ◽  
Margaret Kloster ◽  
Larry C. Lands ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Small Colony Variant ◽  
Small Colony

scholarly journals The ability of Pseudomonas aeruginosa to adopt a Small Colony Variant (SCV) phenotype is conserved, and not restricted to clinical isolates

2021 ◽  
Author(s):  
Alison Besse ◽  
Mylène Trottier ◽  
Marie-Christine Groleau ◽  
Eric Déziel
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Opportunistic Pathogen ◽  
Laboratory Culture ◽  
Culture Conditions ◽  
Health Concern ◽  
Clinical Strain ◽  
Adaptation Mechanism ◽  
Small Colony Variant ◽  
Small Colony

ABSTRACTA subpopulation of Small Colony Variants (SCVs) is a frequently observed feature of Pseudomonas aeruginosa isolated from cystic fibrosis (CF) lungs biofilms. SCVs have almost exclusively been reported from infected hosts, essentially CF individuals or, by extension, from laboratory cultivation of strains originated from infected hosts. We previously reported the identification of P. aeruginosa SCVs emerging from a non-clinical strain and displaying features shared with clinical SCVs. In the present work, we investigated the ability of 22 P. aeruginosa isolates from various environmental origins to, under laboratory culture conditions, spontaneously adopt a SCV-like smaller alternative morphotype distinguishable from the ancestral parent strain. Unexpectedly, we found that all the P. aeruginosa strains tested have the ability to adopt a SCV morphotype, regardless of their origin. Based on the phenotypes already described for SCVs, the SCV-like morphotypes obtained were clustered in two groups displaying various phenotypic profiles, including one characteristic of already described SCVs. We conclude that the ability to switch to a SCV phenotype is a conserved feature in Pseudomonas aeruginosa.IMPORTANCEP. aeruginosa is an opportunistic pathogen that thrives in many environments. It is significant public health concern, notably because it is the most prevalent pathogen found in the lungs of people with cystic fibrosis (CF). In infected hosts, its persistence is believed to be related to the emergence of an alternative small colony variant (SCV) phenotype. By reporting the distribution of P. aeruginosa SCVs in various non-clinical environments, this work contributes to understanding a conserved adaptation mechanism used by P. aeruginosa to rapidly adapt in all environments. Counteraction of this strategy could prevent P. aeruginosa persistent infection in the future.

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