PspA facilitates evasion of pneumococci from bactericidal activity of neutrophil extracellular traps (NETs)

Martinez, Perla J.; Farhan, Anam; Mustafa, Muhammad; Javaid, Nida; Darkoh, Charles; Garrido-Sanabria, Emilio R.; Fisher‐Hoch, Susan P.; Briles, David E.; Kantarcı, Alpdoğan; Mirza, Shaper

doi:10.1016/j.micpath.2019.103653

Cited by 20 publications

(15 citation statements)

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“…Mutants lacking PspA were more susceptible to trapping by NETs, an effect that was dependent on PspA type. In addition, incubation with anti-PspA antibodies promoted NET formation (Martinez et al, 2019). Taken together, the data indicates that PspA is able to directly prevent killing by AMPs, and also to limit the bactericidal mechanisms of neutrophils.…”

Section: Amp Sequestration/inactivationmentioning

confidence: 58%

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Resistance Mechanisms to Antimicrobial Peptides in Gram-Positive Bacteria

et al. 2020

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With the alarming increase of infections caused by pathogenic multidrug-resistant bacteria over the last decades, antimicrobial peptides (AMPs) have been investigated as a potential treatment for those infections, directly through their lytic effect or indirectly, due to their ability to modulate the immune system. There are still concerns regarding the use of such molecules in the treatment of infections, such as cell toxicity and host factors that lead to peptide inhibition. To overcome these limitations, different approaches like peptide modification to reduce toxicity and peptide combinations to improve therapeutic efficacy are being tested. Human defense peptides consist of an important part of the innate immune system, against a myriad of potential aggressors, which have in turn developed different ways to overcome the AMPs microbicidal activities. Since the antimicrobial activity of AMPs vary between Gram-positive and Gram-negative species, so do the bacterial resistance arsenal. This review discusses the mechanisms exploited by Gram-positive bacteria to circumvent killing by antimicrobial peptides. Specifically, the most clinically relevant genera, Streptococcus spp., Staphylococcus spp., Enterococcus spp. and Gram-positive bacilli, have been explored.

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Section: Amp Sequestration/inactivationmentioning

confidence: 58%

“…Pneumococcal surface protein A has also been shown to interfere with the bactericidal activity of NETs (Martinez et al, 2019). Mutants lacking PspA were more susceptible to trapping by NETs, an effect that was dependent on PspA type.…”

Section: Amp Sequestration/inactivationmentioning

confidence: 99%

Resistance Mechanisms to Antimicrobial Peptides in Gram-Positive Bacteria

et al. 2020

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“…PspA is a virulence factor in S. pneumoniae that are involved in the evasion of the complement system [ 57 ]. PspA could also contribute to the resistance of killing by neutrophil extracellular traps (NETs) [ 58 ]. It was also suggested that LysM contributed to the phagocytic resistance of SS2.…”

Section: Discussionmentioning

confidence: 99%

Screening for phagocytosis resistance-related genes via a transposon mutant library of Streptococcus suis serotype 2

et al. 2020

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Streptococcus suis serotype 2 (SS2) is a serious zoonotic pathogen which causes symptoms of streptococcal toxic shock syndrome (STSS) and septicemia; these symptoms suggest that SS2 may have evade innate immunity. Phagocytosis is an important innate immunity process where phagocytosed pathogens are killed by lysosome enzymes, reactive oxygen, and nitrogen species, and acidic environments in macrophages following engulfment. A previously constructed mutant SS2 library was screened, revealing 13 mutant strains with decreased phagocytic resistance. Through inverse PCR, the transposon insertion sites were determined. Through bioinformatic analysis, the 13 disrupted genes were identified as Cps2F , 3 genes belonging to ABC transporters, WalR, TehB, rpiA , S-transferase encoding gene, prs, HsdM , GNAT family N-acetyltransferase encoding gene, proB , and upstream region of DnaK . Except for the capsular polysaccharide biosynthesis associated Cps2F , the other genes had not been linked to a role in anti-phagocytosis. The survival ability in macrophages and whole blood of randomly picked mutant strains were significantly impaired compared with wild-type ZY05719. The virulence of the mutant strains was also attenuated in a mouse infection model. In the WalR mutant, the transcription of HP1065 decreased significantly compared with wild-type strain, indicating WalR might regulated HP1065 expression and contribute to the anti-phagocytosis of SS2. In conclusion, we identified 13 genes that influenced the phagocytosis resistant ability of SS2, and many of these genes have not been reported to be associated with resistance to phagocytosis. Our work provides novel insight into resistance to phagocytosis, and furthers our understanding of the pathogenesis mechanism of SS2.

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“…In animal models, NETs have been shown to play a protector role against bacterial dissemination [84]. However, respiratory pathogens have developed evasion methods through the inhibition of release, degradation, and resistance to NETs [85,86]. It is believed that the excess availability of NETs in the tissues and in the bloodstream causes a harmful effect on the body.…”

Section: Neutrophil Extracellular Trapsmentioning

confidence: 99%

Biomarkers in Community-Acquired Pneumonia (Cardiac and Non-Cardiac)

Méndez

Aldás

Menéndez

2020

JCM

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Community-acquired pneumonia (CAP) remains the first cause of morbidity and mortality worldwide due to infection. Several aspects such as severity and host response are related to its clinical course and outcome. Beyond the acute implications that the infection provokes in the host, pneumonia also has long-term negative consequences. Among them, cardiovascular complications and mortality are the most outstanding. Therefore, an adequate recognition and stratification of the risk of complications and mortality is crucial. Many biomarkers have been studied for these reasons, considering that each biomarker mirrors a different aspect. Moreover, the clinical application of many of them is still being deliberated because of their limitations and the heterogeneity of the disease. In this review, we examine some of the most relevant biomarkers that we have classified as cardiac and non-cardiac. We discuss some classic biomarkers and others that are considered novel biomarkers, which are mainly involved in cardiovascular risk.

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PspA facilitates evasion of pneumococci from bactericidal activity of neutrophil extracellular traps (NETs)

Cited by 20 publications

References 44 publications

Resistance Mechanisms to Antimicrobial Peptides in Gram-Positive Bacteria

Resistance Mechanisms to Antimicrobial Peptides in Gram-Positive Bacteria

Screening for phagocytosis resistance-related genes via a transposon mutant library of Streptococcus suis serotype 2

Biomarkers in Community-Acquired Pneumonia (Cardiac and Non-Cardiac)

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