Mucin Binding to<i>Moraxella catarrhalis</i>during Airway Inflammation Is Dependent on Sialic Acid

Padra, Médea; Benktander, John; Padra, János Tamás; Andersson, Anders; Brundin, Bettina; Tengvall, Sara; Christenson, Karin; Qvarfordt, Ingemar; Gad, Robert; Paulsson, Magnus; Pournaras, N; Lindén, Anders; Lindén, Sara K.

doi:10.1165/rcmb.2021-0064oc

Cited by 7 publications

(11 citation statements)

References 44 publications

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“…Thus, this genus commonly facilitated other pathogens expansion in the gut, including Salmonella typhimurium, Clostridioides difficile and E. coli [34,69]. In the present study, ruminal SA-utilizing commensal Prevotellaceae is depleted [73], while the SA-utilizing opportunistic pathogenic Moraxellaceae is enriched in SARA cows [50], which supports that abnormal SA metabolism facilitates microbial dysbiosis. Notably, Moraxellaceae also enriched in the rumen of clinical and subclinical mastitis cows [49,80], implying its pathogenic effect in mastitis pathogenesis but further research is needed.…”

Section: Discussionsupporting

confidence: 77%

“…LEfSe also confirmed Proteobacteria and Moraxellaceae were enriched in the SRMT group (log 10 LDA score > 3.5, Fig. 11I), which have been reported as the SA-utilizing opportunistic pathogen [50]. Indeed, SRMT increased intestinal sialidase levels compared with those of the control or HRMT groups, while zanamivir treatment reduced sialidase expression compared with that of the SRMT group (Fig.…”

Section: Sara Cows Have Different Ruminal Microbial Compositions and ...supporting

confidence: 54%

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Sialic acid exacerbates gut dysbiosis-associated mastitis through the microbiota-gut-mammary axis by fueling gut microbiota disruption

Zhao

Qiu

et al. 2023

Microbiome

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Background Mastitis is one of the most severe diseases in humans and animals, especially on dairy farms. Mounting evidence indicates that gastrointestinal dysbiosis caused by induction of subacute ruminal acidosis (SARA) by high-grain diet consumption and low in dietary fiber is associated with mastitis initiation and development, however, the underlying mechanism remains unknown. Results In the present study, we found that cows with SARA-associated mastitis have altered metabolic profiles in the rumen, with increased sialic acids level in particular. Consumption of sialic acid (SA) in antibiotic-treated mice, but not healthy mice, induced marked mastitis. SA treatment of antibiotic-treated mice also induced mucosal and systemic inflammatory responses, as evidenced by increased colon and liver injuries and several inflammatory markers. In addition, gut dysbiosis caused by antibiotic impaired gut barrier integrity, which was aggravated by SA treatment. SA potentiated serum LPS level caused by antibiotic treatment, leading to increased activation of the TLR4-NF-κB/NLRP3 pathways in the mammary gland and colon. Moreover, SA facilitated gut dysbiosis caused by antibiotic, and especially enhanced Enterobacteriaceae and Akkermansiaceae, which correlated with mastitis parameters. Fecal microbiota transplantation from SA-antibiotic-treated mice mimicked mastitis in recipient mice. In vitro experiments showed that SA prompted Escherichia coli growth and virulence gene expression, leading to higher proinflammatory cytokine production in macrophages. Targeting the inhibition of Enterobacteriaceae by sodium tungstate or treating with the commensal Lactobacillus reuteri alleviated SA-facilitated mastitis. In addition, SARA cows had distinct ruminal microbial structure by the enrichment of SA-utilizing opportunistic pathogenic Moraxellaceae and the depletion of SA-utilizing commensal Prevotellaceae. Treating mice with the specific sialidase inhibitor zanamivir reduced SA production and Moraxellaceae abundance, and improved mastitis in mice caused by ruminal microbiota transplantation from cows with SARA-associated mastitis. Conclusions This study, for the first time, indicates that SA aggravates gut dysbiosis-induced mastitis by promoting gut microbiota disturbance and is regulated by commensal bacteria, indicating the important role of the microbiota-gut-mammary axis in mastitis pathogenesis and suggesting a potential strategy for mastitis intervention based on gut metabolism regulation.

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Section: Discussionsupporting

confidence: 77%

Section: Sara Cows Have Different Ruminal Microbial Compositions and ...supporting

confidence: 54%

Sialic acid exacerbates gut dysbiosis-associated mastitis through the microbiota-gut-mammary axis by fueling gut microbiota disruption

Zhao

Qiu

et al. 2023

Microbiome

View full text Add to dashboard Cite

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“…Interestingly, Moraxella , Saccharofermentans , Eubacterium_nodatum_group , and Rikenellaceae_RC9_gut_group were abundant, and Prevotella was reduced in the mastitis group compared with the healthy cows. Moraxella is known as a gram-negative pathobiont that causes inflammation, such as airway inflammation [ 48 , 49 ]. We further showed that Moraxella was correlated with mastitis parameters, which agrees with a previous study showing that ruminal Moraxella abundance was changed in cows with mastitis [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Gut dysbiosis induces the development of mastitis through a reduction in host anti-inflammatory enzyme activity by endotoxemia

Zhao

Bao

et al. 2022

Microbiome

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Background Mounting experimental evidence has shown that the gut microbiota plays a significant role in the pathogenesis of mastitis, and clinical investigations have found that the occurrence of mastitis is correlated with ruminal dysbiosis. However, the underlying mechanism by which the ruminal microbiota participates in the development of mastitis remains unknown. Results In the present study, we found that cows with clinical mastitis had marked systemic inflammation, which was associated with significant ruminal dysbiosis, especially enriched Proteobacteria in the rumen. Ruminal microbiota transplantation from mastitis cows (M-RMT) to mice induced mastitis symptoms in recipient mice along with increased mammary proinflammatory signature activation of the TLR4-cGAS-STING-NF-κB/NLRP3 pathways. M-RMT also induced mucosal inflammation and impaired intestinal barrier integrity, leading to increased endotoxemia and systemic inflammation. Moreover, we showed that M-RMT mirrored ruminal microbiota disruption in the gut of recipient mice, as evidenced by enriched Proteobacteria and similar bacterial functions, which were correlated with most proinflammatory parameters and serum lipopolysaccharide (LPS) levels in mice. Recurrent low-grade LPS treatment mirrored gut dysbiosis-induced endotoxemia and caused severe mastitis in mice. Furthermore, we found that gut dysbiosis-derived LPS reduced host alkaline phosphatase activity by activating neuraminidase (Neu), which facilitates low-grade LPS exposure and E. coli-induced mastitis in mice. Conversely, treatment with calf intestinal alkaline phosphatase or the Neu inhibitor zanamivir alleviated low-grade LPS exposure and E. coli-induced mastitis in mice. Conclusions Our results suggest that ruminal dysbiosis-derived low-grade endotoxemia can cause mastitis and aggravate pathogen-induced mastitis by impairing host anti-inflammatory enzymes, which implies that regulating the ruminal or gut microbiota to prevent low-grade systemic inflammation is a potential strategy for mastitis intervention.

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“…catarrhalis to mucus occurs via bacterial binding to Neu5Ac and Neu5Ac-linked glycan structures (e.g. α2–6 sialyllactose; Neu5Ac linked to lactose) within mucus, with this binding correlating with increased inflammation [104]. The human gastric pathogen Helicobacter pylori , responsible for stomach ulcers and gastric cancer, expresses multiple adhesins recognizing glycan structures containing terminal Neu5Ac residues.…”

Section: Attaching To the Host: Sialic Acid As A Cellular Receptor Fo...mentioning

confidence: 99%

How bacteria utilize sialic acid during interactions with the host: snip, snatch, dispatch, match and attach

2022

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N -glycolylneuraminic acid (Neu5Gc), and its precursor N-acetylneuraminic acid (Neu5Ac), commonly referred to as sialic acids, are two of the most common glycans found in mammals. Humans carry a mutation in the enzyme that converts Neu5Ac into Neu5Gc, and as such, expression of Neu5Ac can be thought of as a ‘human specific’ trait. Bacteria can utilize sialic acids as a carbon and energy source and have evolved multiple ways to take up sialic acids. In order to generate free sialic acid, many bacteria produce sialidases that cleave sialic acid residues from complex glycan structures. In addition, sialidases allow escape from innate immune mechanisms, and can synergize with other virulence factors such as toxins. Human-adapted pathogens have evolved a preference for Neu5Ac, with many bacterial adhesins, and major classes of toxin, specifically recognizing Neu5Ac containing glycans as receptors. The preference of human-adapted pathogens for Neu5Ac also occurs during biosynthesis of surface structures such as lipo-oligosaccharide (LOS), lipo-polysaccharide (LPS) and polysaccharide capsules, subverting the human host immune system by mimicking the host. This review aims to provide an update on the advances made in understanding the role of sialic acid in bacteria-host interactions made in the last 5–10 years, and put these findings into context by highlighting key historical discoveries. We provide a particular focus on ‘molecular mimicry’ and incorporation of sialic acid onto the bacterial outer-surface, and the role of sialic acid as a receptor for bacterial adhesins and toxins.

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Mucin Binding toMoraxella catarrhalisduring Airway Inflammation Is Dependent on Sialic Acid

Cited by 7 publications

References 44 publications

Sialic acid exacerbates gut dysbiosis-associated mastitis through the microbiota-gut-mammary axis by fueling gut microbiota disruption

Sialic acid exacerbates gut dysbiosis-associated mastitis through the microbiota-gut-mammary axis by fueling gut microbiota disruption

Gut dysbiosis induces the development of mastitis through a reduction in host anti-inflammatory enzyme activity by endotoxemia

How bacteria utilize sialic acid during interactions with the host: snip, snatch, dispatch, match and attach

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