Interactions of Pseudomonas aeruginosa Proteases with the Cells of the Immune System

Author(s):  
Arsalan Kharazmi
2011 ◽  
Vol 55 (6) ◽  
pp. 2693-2695 ◽  
Author(s):  
G. L. Drusano ◽  
B. VanScoy ◽  
W. Liu ◽  
S. Fikes ◽  
D. Brown ◽  
...  

ABSTRACTOutcomes for patients with dense bacterial burdens, such as ventilator-associated pneumonia (VAP) patients, are often critically influenced by the adequacy of antimicrobial chemotherapy and by the response of the immune system, particularly the granulocytes. Little information is available about the quantitation of kill of organisms over time by granulocytes. In this investigation, we examined the impact of the baseline bacterial burden on the ability of granulocytes alone (without chemotherapy) to keep the number of organisms in check or to kill them over a 24-h period.Pseudomonas aeruginosaATCC 27853 was the study organism, and we employed a murine pneumonia model (granulocyte replete) for the study. We found that the ability of the immune system to killP. aeruginosawas saturable. The burden at which the system was half saturated was 2.15 × 106± 2.66 × 106CFU/g. Burdens greater than 107CFU/g demonstrated net growth over 24 h. These findings suggest the need for aggressive chemotherapy early in the treatment of VAP to keep the burden from saturating the granulocytes. This should optimize the outcome for these seriously infected patients.


2010 ◽  
Vol 78 (11) ◽  
pp. 4744-4753 ◽  
Author(s):  
Tamding Wangdi ◽  
Lilia A. Mijares ◽  
Barbara I. Kazmierczak

ABSTRACT Microbe-associated molecular patterns are recognized by Toll-like receptors of the innate immune system. This recognition enables a rapid response to potential pathogens but does not clearly provide a way for the innate immune system to discriminate between virulent and avirulent microbes. We find that pulmonary infection of mice with type 3 translocation-competent Pseudomonas aeruginosa triggers a rapid inflammatory response, while infection with isogenic translocation-deficient mutants does not. Discrimination between translocon-positive and -negative bacteria requires caspase-1 activity in bone marrow-derived cells and interleukin-1 receptor signaling. Thus, the activation of caspase-1 by bacteria expressing type 3 secretion systems allows for rapid recognition of bacteria expressing conserved functions associated with virulence.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1740
Author(s):  
Elena Trizna ◽  
Diana Baidamshina ◽  
Anna Gorshkova ◽  
Valentin Drucker ◽  
Mikhail Bogachev ◽  
...  

While in a biofilm, bacteria are extremely resistant to both antimicrobials and the immune system, leading to the development of chronic infection. Here, we show that bovine hyaluronidase fused with a copolymer of 1,4-ethylenepiperazine N-oxide and (N-carboxymethyl) -1,4-ethylenepiperazinium bromide (Longidaza®) destroys both mono- and dual-species biofilms formed by various bacteria. After 4 h of treatment with 750 units of the enzyme, the residual biofilms of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae preserved about 50–70% of their initial mass. Biomasses of dual-species biofilms formed by S. aureus and the four latter species were reduced 1.5-fold after 24 h treatment, while the significant destruction of S. aureus–P. aeruginosa and S. aureus–K. pneumoniae was also observed after 4 h of treatment with Longidaza®. Furthermore, when applied in combination, Longidaza® increased the efficacy of various antimicrobials against biofilm-embedded bacteria, although with various increase-factor values depending on both the bacterial species and antimicrobials chosen. Taken together, our data indicate that Longidaza® destroys the biofilm structure, facilitating the penetration of antimicrobials through the biofilm, and in this way improving their efficacy, lowering the required dose and thus also potentially reducing the associated side effects.


2020 ◽  
Vol 203 (2) ◽  
pp. e00300-20
Author(s):  
Katie V. Farrant ◽  
Livia Spiga ◽  
Jane C. Davies ◽  
Huw D. Williams

ABSTRACTPseudomonas aeruginosa is a significant nosocomial pathogen and is associated with lung infections in cystic fibrosis (CF). Once established, P. aeruginosa infections persist and are rarely eradicated despite host immune cells producing antimicrobial oxidants, including hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). There is limited knowledge as to how P. aeruginosa senses, responds to, and protects itself against HOCl and HOSCN and the contribution of such responses to its success as a CF pathogen. To investigate the P. aeruginosa response to these oxidants, we screened 707 transposon mutants, with mutations in regulatory genes, for altered growth following HOCl exposure. We identified regulators of antibiotic resistance, methionine biosynthesis, catabolite repression, and PA14_07340, the homologue of the Escherichia coli HOCl-sensor RclR (30% identical), which are required for protection against HOCl. We have shown that RclR (PA14_07340) protects specifically against HOCl and HOSCN stress and responds to both oxidants by upregulating the expression of a putative peroxiredoxin, rclX (PA14_07355). Transcriptional analysis revealed that while there was specificity in the response to HOCl (231 genes upregulated) and HOSCN (105 genes upregulated), there was considerable overlap, with 74 genes upregulated by both oxidants. These included genes encoding the type 3 secretion system, sulfur and taurine transport, and the MexEF-OprN efflux pump. RclR coordinates part of the response to both oxidants, including upregulation of pyocyanin biosynthesis genes, and, in the presence of HOSCN, downregulation of chaperone genes. These data indicate that the P. aeruginosa response to HOCl and HOSCN is multifaceted, with RclR playing an essential role.IMPORTANCE The bacterial pathogen Pseudomonas aeruginosa causes devastating infections in immunocompromised hosts, including chronic lung infections in cystic fibrosis patients. To combat infection, the host’s immune system produces the antimicrobial oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). Little is known about how P. aeruginosa responds to and survives attack from these oxidants. To address this, we carried out two approaches: a mutant screen and transcriptional study. We identified the P. aeruginosa transcriptional regulator, RclR, which responds specifically to HOCl and HOSCN stress and is essential for protection against both oxidants. We uncovered a link between the P. aeruginosa transcriptional response to these oxidants and physiological processes associated with pathogenicity, including antibiotic resistance and the type 3 secretion system.


2003 ◽  
Vol 95 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Hernan Aviles ◽  
Tesfaye Belay ◽  
Kimberly Fountain ◽  
Monique Vance ◽  
Gerald Sonnenfeld

It has been reported that spaceflight conditions alter the immune system and resistance to infection [Belay T, Aviles H, Vance M, Fountain K, and Sonnenfeld G. J Allergy Clin Immunol 170: 262–268, 2002; Hankins WR and Ziegelschmid JF. In: Biomedical Results of Apollo. Washington, DC: NASA, 1975, p. 43–81 . (NASA Spec. Rep. SP-368)]. Ground-based models, including the hindlimb-unloading model, have become important tools for increasing understanding of how spaceflight conditions can influence physiology. The objective of the present study was to determine the effect of hindlimb unloading on the susceptibility of mice to Pseudomonas aeruginosa infection. Hindlimb-unloaded and control mice were subcutaneously infected with 1 LD50 of P. aeruginosa. Survival, bacterial organ load, and antibody and corticosterone levels were compared among the groups. Hindlimb unloading had detrimental effects for infected mice. Animals in the hindlimb-unloaded group, compared with controls, 1) showed significantly increased mortality and reduced time to death, 2) had increased levels of corticosterone, and 3) were much less able to clear bacteria from the organs. These results suggest that hindlimb unloading may induce the production of corticosterone, which may play a critical role in the modulation of the immune system leading to increased susceptibility to P. aeruginosa infection.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Lei Feng ◽  
Qingqing Xiang ◽  
Qing Ai ◽  
Zhengli Wang ◽  
Yunhui Zhang ◽  
...  

Background. Quorum sensing (QS) systems play an important role in modulating biofilm formation. Recent studies have found that the QS molecules had complex effects on the host immune systems. In addition, regulatory T cells (Tregs), known as important negative regulators in the immune system, have been found upregulated in multiple chronic infections. Therefore, the QS systems were hypothesized to be involved in modulating Tregs in biofilm-associated infections.Object. To explore the effects of QS systems on Tregs in catheter-relatedPseudomonas aeruginosabiofilm infection rat models.Method. Catheter-relatedPseudomonas aeruginosabiofilm infection rat models were established; the bacterial clearance rates, total cell counts in bronchoalveolar lavage (BAL) fluid, pathological changes of lungs, and the levels of Foxp3, TGF-β1, and IL-10 in PAO1 strain group were examined and compared with the QS-mutant ΔlasRΔrhlRandΔlasIΔrhlIgroups.Results. In PAO1 group, the bacterial clearance rates were lower, total cell counts were higher, pathological changes were severer, and the levels of Foxp3, TGF-β1, and IL-10 were significantly higher compared with QS-mutant groups(p<0.05). No significant difference was observed between the two QS-mutant groups(p>0.05).Conclusion. QS systems can trigger host immune system, accompanied with the upregulation of Tregs.


2012 ◽  
Vol 194 (21) ◽  
pp. 5728-5738 ◽  
Author(s):  
K. C. Cady ◽  
J. Bondy-Denomy ◽  
G. E. Heussler ◽  
A. R. Davidson ◽  
G. A. O'Toole

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0181932 ◽  
Author(s):  
Gabriel Torrens ◽  
Marcelo Pérez-Gallego ◽  
Bartolomé Moya ◽  
Marta Munar-Bestard ◽  
Laura Zamorano ◽  
...  

2015 ◽  
Vol 4 (3) ◽  
Author(s):  
Daslina Daslina ◽  
Eryati Darwin ◽  
Aziz Djamal

Abstrak Pseudomonas aeruginosa adalah bakteri penyebab infeksi terbanyak yang resisten terhadap antibiotik. Glutamin adalah asam amino yang terdapat dalam tubuh yang salah satu fungsinya dapat memodulasi imunitas tubuh. Tujuan penelitian ini adalah menentukan potensi glutamin dalam meningkatkan kemampuan sistem imun terhadap infeksi P. aeruginosa. Penelitian eksperimental dengan post test only control group design telah dilakukan terhadap 24 ekor mencit usia 6-8 minggu dengan berat 30 gr. Mencit dibagi ke dalam dua kelompok, yaitu kontrol (K) danperlakuan (P) yang diberi glutamin dengan dosis 30 mg/kg/hari selama 14 hari. Isolasi makrofag peritoneum mencit dilakukan pada hari ke-15 dan dilakukan uji fagositosis menggunakan latex dan bakteri P. aeruginosa. Pengamatan dilakukan terhadap persentase makrofag aktif terhadap latex dan P. aeruginosa. Hasil pengamatan dan analisisstatistik menggunakan metode t-test menunjukkan adanya perbedaan yang signifikan antara kontrol dan perlakuan (p<0.05). Persentase makrofag aktif terhadap latex adalah 0,63 ± 0,058 (K) dan 0,84 ± 0,04 (P), sedangkan terhadap P. aeruginosa adalah 0,56± 0,07 (K) dan 0,80± 0,03 (P). Terlihat bahwa angka persentase fagositosis terhadap P.aeruginosa lebih kecil karena adanya kemampuan bakteri untuk menghadapi makrofag dibandingkan latex. Kesimpulan yang diperoleh dari penelitian ini adalah bahwa asam amino non-esensial glutamin memiliki pengaruh untuk meningkatkan kemampuan sistem imun tubuh. Kata kunci: glutamin, fagositosis makrofag, Pseudomonas aeruginosa Abstract Pseudomonas aeruginosa is the most common cause of bacterial infections that are resistant to antibiotics. Glutamine is an amino acid  in the body that able to modulate the body's immune function. The objective of this study was to determine the potential of glutamine in enhancing the ability of the immune system against infection of P.aeruginosa. Experimental research with post test only control group design was conducted on 24 male minutes 6-8 weeks of age weighing 30 grams. Mice were divided into two groups: control (K) and treatment (P) are given glutamine at a dose of 30 mg / kg / day for 14 days. Isolation of peritoneal macrophages of mice performed on day-15 and testedusing latex and bacterial phagocytosis of P. aeruginosa. Observations were made of the percentage of activated macrophages toward latex and P. aeruginosa. The observation result and statistical analysis using t -test showed a significant difference between the control and treatment (p <0.05). The percentage of active macrophages to latex was0.63 ± 0.058 (K) and 0.84 ± 0.04 (P), while to P. aeruginosa is 0.56 ± 0.07 (K) and 0.80 ± 0.03 (P). That seein it percentage of phagocytosis against P. aeruginosa smaller than compared to latex. Because of the ability of bacteria to confront macrophages. The conclusion from this study is a non-essensial amino acid glutamine has the effect to increase the ability of the body's immune system. Keywords: glutamin, immunity phagocytosis macrophage, Pseudomonas aeruginosa 


2020 ◽  
Vol 97 (1) ◽  
pp. 83-90
Author(s):  
N. M. Shlepotina ◽  
M. V. Peshikova ◽  
O. L. Kolesnikov ◽  
Yu. S. Shishkova

Features of the cellular immune response in the presence of a microbial biofilm are well described in the literature. Based on numerous studies, it became possible to establish a number of patterns: mature biofilms are better protected from immune factors, the effectiveness of antibiofilm strategies depends on species of the microorganisms, forming the biofilm, and, accordingly, on the composition of the biopolymer matrix. For example, rhamnolipids and alginate of Pseudomonas aeruginosa exert a significant negative effect on the function of immunocompetent cells. The bacteria of biofilms became able to turn to their advantage many of the protective reactions developed by the immune system and fixed evolutionarily, applying them for the growth and development of the microbial consortium.


Sign in / Sign up

Export Citation Format

Share Document