The Role of Bacterial Lipopolysaccharides as Immune Modulator in Vaccine and Drug Development

Arenas, Jesús

doi:10.2174/187153012802002884

Cited by 25 publications

(17 citation statements)

References 154 publications

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“…LPS-neutralizing antibodies can inhibit immune responses such as the TLR-4 dependent response elicited by lipid A, but the development of such molecules is hampered by a plethora of serotypes. The inner core region is an interesting target for therapeutic antibodies, as this region is more conserved (188)(189)(190). Recent antimicrobial approaches have focused on lipid A antagonists, such as Eritoran, that can block these proinflammatory responses (191).…”

Section: Fig 6 O-antigen Lps Biosynthesis and Lps Assembly And Transpmentioning

confidence: 99%

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

Tytgat

Lebeer

2014

Microbiol Mol Biol Rev

126

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SUMMARY Humans have been increasingly recognized as being superorganisms, living in close contact with a microbiota on all their mucosal surfaces. However, most studies on the human microbiota have focused on gaining comprehensive insights into the composition of the microbiota under different health conditions (e.g., enterotypes), while there is also a need for detailed knowledge of the different molecules that mediate interactions with the host. Glycoconjugates are an interesting class of molecules for detailed studies, as they form a strain-specific barcode on the surface of bacteria, mediating specific interactions with the host. Strikingly, most glycoconjugates are synthesized by similar biosynthesis mechanisms. Bacteria can produce their major glycoconjugates by using a sequential or an en bloc mechanism, with both mechanistic options coexisting in many species for different macromolecules. In this review, these common themes are conceptualized and illustrated for all major classes of known bacterial glycoconjugates, with a special focus on the rather recently emergent field of glycosylated proteins. We describe the biosynthesis and importance of glycoconjugates in both pathogenic and beneficial bacteria and in both Gram-positive and -negative organisms. The focus lies on microorganisms important for human physiology. In addition, the potential for a better knowledge of bacterial glycoconjugates in the emerging field of glycoengineering and other perspectives is discussed.

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Section: Fig 6 O-antigen Lps Biosynthesis and Lps Assembly And Transpmentioning

confidence: 99%

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

Tytgat

Lebeer

2014

Microbiol Mol Biol Rev

126

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“…Lipopolysaccharide (LPS), a major component of gram-negative bacteria cell wall, is broadly used as a bacterial infection mimic to induce a systemic inflammatory response [13]. LPS compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells and worsens murine experimental stroke [12].…”

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confidence: 99%

Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

Hu¹,

Doll²,

Sun³

et al. 2016

Aging and disease

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Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post-stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS-stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for stroke severity in experimental stroke animal models and may have translational significance for clinical stroke patients -targeting endothelial mitochondria may be a clinically useful approach for stroke therapy.

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“…In parallel, inhibitors targeting enzymes involved in KDO biosynthesis were also explored (Cipolla et al 2011); some have potent inhibitor capabilities, but their use was restricted for several reasons such as inhibition of enzymes present in the host, reduced accessibility of the enzyme, and development of resistance. Besides this strategy, a series of hTLR4 antagonists (natural Lipid A and synthetic analogous of Lipid A with reduced numbers of acyl chains) were proposed to neutralize the effects of endotoxin by inhibiting hTLR4 signaling (Arenas 2012). They act at different levels of the sequential LPS transfer by targeting components of the LPS recognition system (LBP, CD14, MD-2 and TLR4).…”

Section: Modulation By Drugsmentioning

confidence: 99%

“…In part, they have been used in conjunction with available adjuvants, such as aluminum hydroxide and detergent emulsions, while low-toxicity LPS variants are being used in the production of OM vesicle (OMV)-based vaccines. As a potential adjuvant, LPS activates Th1 type T cell differentiation, while standard adjuvants activate Th2 type cells, the former being necessary for suitable protection in therapies against several diseases (i.e., certain viruses, cancer, or allergy) (Arenas 2012). In fact, the LPS derivative monophosphoryl Lipid A is included in two approved vaccines against allergy and cancer.…”

Section: Modulation By Drugsmentioning

confidence: 99%

Bacterial Lipopolysaccharide

Arenas¹

2014

Encyclopedia of Inflammatory Diseases

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The Role of Bacterial Lipopolysaccharides as Immune Modulator in Vaccine and Drug Development

Cited by 25 publications

References 154 publications

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

Bacterial Lipopolysaccharide

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