Pneumococcal lipoproteins involved in bacterial fitness, virulence, and immune evasion

Abstract

Edited by Wilhelm JustStreptococcus pneumoniae (pneumococcus) has evolved sophisticated strategies to survive in several niches within the human body either as a harmless commensal or as a serious pathogen causing a variety of diseases. The dynamic interaction between pneumococci and resident host cells during colonization of the upper respiratory tract and at the site of infection is critical for bacterial survival and the development of disease. Pneumococcal lipoproteins are peripherally anchored membrane proteins and have pivotal roles in bacterial fitness including envelope stability, cell division, nutrient acquisition, signal transduction, transport (as substrate-binding proteins of ABC transporter systems), resistance to oxidative stress and antibiotics, and protein folding. In addition, lipoproteins are directly involved in virulence-associated processes such as adhesion, colonization, and persistence through immune evasion. Conversely, lipoproteins are also targets for the host response both as ligands for toll-like receptors and as targets for acquired antibodies. This review summarizes the multifaceted roles of selected pneumococcal lipoproteins and how this knowledge can be exploited to combat pneumococcal infections.

Proteomic Investigation Uncovers Potential Targets and Target Sites of Pneumococcal Serine-Threonine Kinase StkP and Phosphatase PhpP

“…In addition to that the emergence of antimicrobial resistance in bacterial infections has become a major public health concern worldwide. The pneumococcus overcomes not only the stress and starvation conditions of the ever-dynamic settings of bacterial habitats, but also the host defense mechanisms and antibiotic treatments (Koppe et al, 2012;Saleh et al, 2013;Kohler et al, 2016;Rabes et al, 2016). Additionally, S. pneumoniae is increasingly resistant to the most common clinically used drugs such as beta-lactam antibiotics and macrolides (Schulz and Hammerschmidt, 2013;Gladstone et al, 2019;Peyrani et al, 2019).…”

“…Moreover, it can express a high number of specific virulence factors that raise pathogenicity by complex mechanisms (Bogaert et al, 2004;Kadioglu et al, 2008;Gamez and Hammerschmidt, 2012;Voss et al, 2012;Doran et al, 2016;Loughran et al, 2019;Subramanian et al, 2019). To ensure successful treatments in the future, it is vital to develop new antimicrobial drugs against pneumococci and their resistant strains, which are not based on the composition of the polysaccharide capsule but on other virulence factors like specific proteins, e.g., choline-binding proteins or lipoproteins (Pérez-Dorado et al, 2012;Kohler et al, 2016;Voß et al, 2018). Basic research of pneumococcal protein regulation is therefore required to decipher the molecular and cellular mechanisms that underlie pathogenesis and virulence.…”

Selective substrate uptake: The role of ATP-binding cassette (ABC) importers in pathogenesis

“…MetQ is the SBP of the methionine-uptake MetQNP ABC transporter in S. pneumoniae , and is another serotype-specific virulence factor [89]. Coinfection of wildtype and ΔmetQ strains of S. pneumoniae serotype 3 clinical isolate 0100993 showed attenuated colonization of the metQ mutant in the nasopharynx and spleens of CD1 mice [90].…”

Deletion of the Zinc Transporter Lipoprotein AdcAII Causes Hyperencapsulation of Streptococcus pneumoniae Associated with Distinct Alleles of the Type I Restriction-Modification System

“…The degree of capsule expression by S. pneumoniae is also affected by phase variation at different sites of infection (9,10). Opaque-phase S. pneumoniae has increased thickness of the capsule layer and is associated with invasive infections such as septicemia, whereas transparent-phase S. pneumoniae has thinner capsule layers and is associated with colonization and biofilm formation (11)(12)(13). Despite the importance of capsule expression during S. pneumoniae interactions with the host, the molecular mechanisms underpinning phase variation and capsule thickness remain relatively poorly understood.…”