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Background: Methanogenic archaea represent a less investigated and likely underestimated part of the intestinal tract microbiome in swine.
Aims/Methods: This study aims to elucidate the archaeome structure and function in the porcine intestinal tract of healthy and H1N1 infected swine. We performed multi-omics analysis consisting of 16S rRNA gene profiling, metatranscriptomics and metaproteomics.
Results and discussion: We observed a significant increase from 0.48 to 4.50% of archaea in the intestinal tract microbiome along the ileum and colon, dominated by genera Methanobrevibacter and Methanosphaera. Furthermore, in feces of naïve and H1N1 infected swine, we observed significant but minor differences in the occurrence of archaeal phylotypes over the course of an infection experiment. Metatranscriptomic analysis of archaeal mRNAs revealed the major methanogenesis pathways of Methanobrevibacter and Methanosphaera to be hydrogenotrophic and methyl-reducing, respectively. Metaproteomics of archaeal peptides indicated some effects of the H1N1 infection on central metabolism of the gut archaea.
Conclusions/Take home message: Finally, this study provides the first multi-omics analysis and high-resolution insights into the structure and function of the porcine intestinal tract archaeome during a non-lethal Influenza A virus infection of the respiratory tract, demonstrating significant alterations in archaeal community composition and central metabolic functions.
Proteomic Adaptation of Clostridioides difficile to Treatment with the Antimicrobial Peptide Nisin
(2021)
Infections with bacterial pathogens are a major cause of morbidity and mortality
worldwide. Furthermore, the extensive use of antibiotics increased the frequency of infections with drug-resistant pathogens. Streptococcus pneumoniae, a major cause of
bacterial pneumonia, is among the pathogens that often show resistances. As an
additional side effect, the use of antibiotics can disrupt the patient’s intestinal microbiome, allowing Clostridioides difficile to cause severe, recurring and hard-to-treat
colitis. Hence, new antimicrobials are needed to combat infections caused by these
pathogens. A promising approach is the usage of antimicrobial peptides (AMPs), defense
molecules produced by organisms from all domains of life. AMPs can specifically perforate
bacterial membranes and stimulate the overall immune response of the host.
In this work, the proteomic adaptations of S. pneumoniae to the human antimicrobial
peptides LL-37 and hBD3 were assessed by high-resolution mass spectrometry and
compared to general membrane stress, in order to evaluate the specificity of the bacterial
reactions. Furthermore, C. difficile was challenged with the Lactococcus lactis-derived
AMP nisin, and the proteomic alterations were examined. In essence, application of LL-37
and hBD3 changed the abundance of pneumococcal proteins involved in membrane
transport, including a putative AMP transporter, a protease, virulence proteins and
genetic regulators. Moreover, a challenge with LL-37 caused an increase of proteins
involved in cell surface modifications that alter the bacterial membrane charge and repel cationic molecules such as LL-37. In support of this, mutants unable to express these
proteins were more sensitive to LL-37. In contrast, general membrane stress, induced by
the application of cationic detergents, produced a diverse proteomic adjustment, though the same two-component regulatory system was activated. In C. difficile, levels of flagella proteins were significantly increased shortly after treatment with nisin, being in
accordance with subsequent electron microscopy data and pointing at a role of these
proteins in adaptation to nisin. Interestingly, a flagella-overexpressing mutant showed an
enhanced resistance towards nisin, independent of bacterial motility.
Taken together, the bacterial pathogens under investigation seem to possess
mechanisms to reduce the effect of AMPs on their physiology, a finding that should be
considered developing drugs based on AMPs. Although AMPs exhibit membrane
perturbations as a common mechanism of action, bacterial adaptation to AMPs appear
multifactorial and dependent on the exact pathogen observed and AMP used.