Neuraminidase A-Exposed Galactose Promotes Streptococcus pneumoniae Biofilm Formation during Colonization.

Streptococcus pneumoniae is an opportunistic pathogen that colonizes the nasopharynx. Herein we show that carbon availability is distinct between the nasopharynx and bloodstream of adult humans: glucose is absent from the nasopharynx, whereas galactose is abundant. We demonstrate that pneumococcal neuraminidase A (NanA), which cleaves terminal sialic acid residues from host glycoproteins, exposed galactose on the surface of septal epithelial cells, thereby increasing its availability during colonization. We observed that S. pneumoniae mutants deficient in NanA and ß-galactosidase A (BgaA) failed to form biofilms in vivo despite normal biofilm-forming abilities in vitro Subsequently, we observed that glucose, sucrose, and fructose were inhibitory for biofilm formation, whereas galactose, lactose, and low concentrations of sialic acid were permissive. Together these findings suggested that the genes involved in biofilm formation were under some form of carbon catabolite repression (CCR), a regulatory network in which genes involved in the uptake and metabolism of less-preferred sugars are silenced during growth with preferred sugars. Supporting this notion, we observed that a mutant deficient in pyruvate oxidase, which converts pyruvate to acetyl-phosphate under non-CCR-inducing growth conditions, was unable to form biofilms. Subsequent comparative transcriptome sequencing (RNA-seq) analyses of planktonic and biofilm-grown pneumococci showed that metabolic pathways involving the conversion of pyruvate to acetyl-phosphate and subsequently leading to fatty acid biosynthesis were consistently upregulated during diverse biofilm growth conditions. We conclude that carbon availability in the nasopharynx impacts pneumococcal biofilm formation in vivo Additionally, biofilm formation involves metabolic pathways not previously appreciated to play an important role.

Current therapies in treatment and prevention of fracture wound biofilms: why a multifaceted approach is essential for resolving persistent infections.

Traumatic orthopedic injuries, particularly extremity wounds, are a significant cause of morbidity. Despite prophylactic antibiotic treatment and surgical intervention, persistent infectious complications can and do occur. Persistent bacterial infections are often caused by biofilms, communities of antibiotic tolerant bacteria encased within a matrix. The structural and metabolic differences in this mode of growth make treatment difficult. Herein, we describe both established and novel, experimental treatments targeted at various stages of wound healing that are specifically aimed at reducing and eliminating biofilm bacteria. Importantly, the highly tolerant nature of these bacterial communities suggests that most singular approaches could be circumvented and a multifaceted, combinatorial approach will be the most effective strategy for treating these complicated infections.

Inhibition of fracture healing in the presence of contamination by Staphylococcus aureus: Effects of growth state and immune response.

Extremity injuries comprise a significant portion of trauma, affecting quality of life, financial burden, and return to duty. Bacterial contamination is commonly associated with failure to heal, despite antibiotic treatment, suggesting that additional therapies must be developed to combat these complications. Treatment failure is likely due to the presence of resistant microbial communities known as biofilms. Biofilm bacteria are able to elicit a direct inhibition of healing through a multitude of known factors. However, they likely also inhibit healing through alteration of the inflammatory response. As inflammation is a critical step in fracture healing, how the presence of biofilm bacteria shifts this response to one that is suboptimal for healing is an important consideration that is currently understudied. The profile of inflammatory factors in response to biofilm bacteria is unique and distinct from those induced during normal healing or by planktonic bacteria alone. This review will examine the presence of inflammatory factors during normal healing and those induced by contaminating bacteria, and will discuss how these differences may ultimately lead to nonunion. Specifically, this review will focus on the Th1/Th2/Th17 type inflammatory responses and how shifts in the balance of these responses during infection can lead to both ineffective clearance and disruption of fracture healing. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1845-1854, 2017.

Future perspective on host-pathogen interactions during bacterial biofilm formation within the nasopharynx.

Nasopharyngeal colonization provides bacteria with a place of residence, a platform for person-to-person transmission and for many opportunistic pathogens it is a prerequisite event towards the development of invasive disease. Therefore, how host factors within the nasopharynx contribute to, inhibit or otherwise shape biofilm formation, the primary mode of existence for colonizing bacteria, and how biofilm bacteria subvert the acute inflammatory response that facilitates clearance, are important topics for future microbiological research. This review proposes the examination of host components as bridging molecules for bacterial interactions during biofilm formation, altered virulence determinant production and cell wall modification as a mechanism for immunoquiescence, and the role of host factors as signals and co-opted mechanisms for bacterial dissemination, together providing an opportunity for disease.