Molecular Mechanisms That Define Redox Balance Function in Pathogen-Host Interactions—Is There a Role for Dietary Bioactive Polyphenols?

Abstract

To ensure a functional immune system, the mammalian host must detect and respond to the presence of pathogenic bacteria during infection. This is accomplished in part by generating reactive oxygen species (ROS) that target invading bacteria; a process that is facilitated by NADPH oxidase upregulation. Thus, bacterial pathogens must overcome the oxidative burst produced by the host innate immune cells in order to survive and proliferate. In this way, pathogenic bacteria develop virulence, which is related to the affinity to secrete effector proteins against host ROS in order to facilitate microbial survival in the host cell. These effectors scavenge the host generated ROS directly, or alternatively, manipulate host cell signaling mechanisms designed to benefit pathogen survival. The redox-balance of the host is important for the regulation of cell signaling activities that include mitogen-activated protein kinase (MAPK), p21-activated kinase (PAK), phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor κB (NF-κB) pathways. An understanding of the function of pathogenic effectors to divert host cell signaling is important to ascertain the mechanisms underlying pathogen virulence and the eventual host–pathogen relationship. Herein, we examine the effectors produced by the microbial secretion system, placing emphasis on how they target molecular signaling mechanisms involved in a host immune response. Moreover, we discuss the potential impact of bioactive polyphenols in modulating these molecular interactions that will ultimately influence pathogen virulence.

Rare by Natural Selection: Tunable Disulfide-bonded Supramolecular Antimicrobials Peptides

“…Their dependence on oxidizing conditions can also be used to target activity of AMPs to act on cancerous cells 54 . It is possible that the observed selection against sahAMPs with an odd number of cysteine residues is due to the microorganisms' ability to express reducing factors [25][26][27] . Since AMP self-assembly can often bear functional relevance and enhance antimicrobial activity 33 , another explanation to this negative selection could be that the intermolecular disulfide bonds lead to a reduction in the number of conformational states, and to reduced entropy, similarly to disulfide-mediated protein folding [55][56][57][58][59][60] , thereby hindering peptide aggregation.…”

“…For example, in-vivo cleavage of host AMPs can lead to truncated forms with a diverse array of activities and selectivity against microbial strains, alongside additional functions within the immune system 6,[8][9][10][11][12][13][14][15][16] . Furthermore, secretion of reducing and oxidizing factors can regulate the activity of cysteine-containing AMPs that form disulfide bonds essential for their folding and activity [16][17][18][19][20][21][22][23][24][25][26][27][28] . For instance, pro-inflammatory processes involve oxidative stress through elevating reactive oxygen species (ROS) concentrations [23][24][25]29 .…”

“…For instance, pro-inflammatory processes involve oxidative stress through elevating reactive oxygen species (ROS) concentrations [23][24][25]29 . In parallel, some pathogens can promote and express reducing factors that diffuse the oxidativedependent processes of inflammation and affect the activity of cysteine-rich AMPs 25,26,30 .…”

Chalcones Display Anti-NLRP3 Inflammasome Activity in Macrophages through Inhibition of Both Priming and Activation Steps—Structure-Activity-Relationship and Mechanism Studies

“…Chalcones and flavonoids, which are various compounds found naturally throughout fruits and vegetables, are always responsible for biological activity and therapeutic efficacy of herbs in treating and preventing a variety of diseases, such as cancer, atherosclerosis, diabetes, hepatotoxicity, bacterial infection, and inflammation [ 1 , 2 , 3 , 4 ]. There are thousands of studies reporting that chalcones and flavonoids display biological activities in diverse in vitro and in vivo models through regulating multiple signaling pathways, including mitogen-activated protein kinases [MAPKs, e.g., Erk1/2, p38 MAPK and c-Jun N-terminal kinase (JNK)], nuclear factor-ĸB (NF-ĸB), phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), Janus kinase (JAK)/signal transducers and activators of transcription (STAT), cyclic nucleotide dependent protein kinases, intracellular calcium mobilization, and oxidative stress proteins [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. The fundamental capability of these compounds is the inhibition of inflammation, which has been linked to most of the diseases.…”

The Role of Reactive Oxygen Species and Nitric Oxide in the Inhibition of Trichophyton rubrum Growth by HaCaT Cells

“…Many studies have demonstrated that external stimuli, such as phototherapy or host cell defense, trigger the production of reactive oxygen species (ROS) and nitric oxide (NO) in fungal cells, which are molecules that appear to be critical for killing T. rubrum [12,13]. The fate of the fungus during this exposure to external stress is dependent on free radicals, especially ROS and NO [14].…”