There is a specific response to pH by isolates of Haemophilus influenzae and this has a direct influence on biofilm formation

Abstract

BackgroundHaemophilus influenzae colonizes the nasopharynx as a commensal. Strain-specific factors allow some strains to migrate to particular anatomical niches, such as the middle ear, bronchi or blood, and induce disease by surviving within the conditions present at these sites in the body. It is established that H. influenzae colonization and in some cases survival is highly dependent on their ability to form a biofilm. Biofilm formation is a key trait in the development of chronic infection by certain isolates. This is exemplified by the contrast between the biofilm-forming strains found in middle ear infections and those isolates that survive within the blood and are rarely associated with biofilm development.ResultsScreening a group of H. influenzae strains revealed only slight variations in their growth across a range of pH conditions. However, some isolates responded to a pH of 8.0 by the formation of a biofilm. While the type b capsular blood isolate Eagan did not form a biofilm and grew at the same rate regardless of pH 6.8-8.0, transcriptomic analyses demonstrated that at pH 8.0 it uniquely induced a gluconate-uptake and metabolism pathway, which concurrently imports H+. A non-typeable H. influenzae, isolated from the middle ear, induced biofilm formation at pH 8.0, and at this pH it induced a series of iron acquisition genes, consistent with previous studies linking iron homeostasis to biofilm lifestyle.ConclusionsDifferent strains of H. influenzae cope with changes in environmental factors using strain-specific mechanisms. These pathways define the scope and mode of niche-survival for an isolate. The pH is a property that is different from the middle ear (at least pH 8.0) compared to other sites that H. influenzae can colonize and infect. The transcriptional response to increasing pH by H. influenzae varies between strains, and pH is linked to pathways that allow strains to either continue free-living growth or induction of a biofilm. We showed that a biofilm-forming isolate induced iron metabolism pathways, whereas a strain that does not form biofilm at increasing pH induced mechanisms for growth and pH homeostasis based on sugar acid transport.

Effect of pH and oxygen on biofilm formation in acute otitis media associated NTHi clinical isolates

“…It is well known that purulent material has a low pH . Prior studies have measured pH in MEF of children with OME and the effect of pH in an in vitro assay of biofilm formation . To our knowledge, this is the first study where measurement of MEF at onset of AOM has been documented and dual pH and oxygen concentration effects on biofilm formation studied.…”

“…At onset and during the pathologic process of AOM, the middle ear space becomes filled with neutrophils (pus), and it is reasonable to postulate that normal atmospheric pressure and gaseous conditions in the middle ear exist, and that fluctuations in these gaseous conditions and pH occur concurrently or independently of each other and may promote biofilm formation. With rAOM and when OME develops, middle ear fluid (MEF) may exist in a reduced oxygen state and a pH environment that promotes biofilm formation by some NTHi strains in the middle ear …”

“…To our knowledge, this is the first study where measurement of MEF at onset of AOM has been documented and dual pH and oxygen concentration effects on biofilm formation studied. Also, there has been only one prior study of multiple clinical pediatric isolates to determine if all strains form biofilms under conditions as might exist in children during AOM or OME …”

Letter to the Editor: Editor's Spotlight/Take 5: Is Single-stage Revision According to a Strict Protocol Effective in Treatment of Chronic Knee Arthroplasty Infections

“…In short, the biofilm allows the bacteria to control the environment like a bio-dome. We now know that at least some biofilms can be impacted by pH [5]. Perhaps this is a vice versa situation with each having the ability to impact the other.…”

Effects of nucleotide usage on the synonymous codon usage patterns of biofilm-associated genes in Haemophilus parasuis

“…Although H. parasuis only infects pigs, it has caused significantly increased mortality and morbidity rates, leading to major economic losses in the pig-rearing industry . Because of its ability to form biofilms, H. parasuis colonies are resilient and exhibit high survival rates (Ishak et al, 2014). Bacterial cells enclosed in the selfproduced polymer matrix form the biofilm; the polymer matrix is composed of proteins, nucleic acids, and exopolysaccharides.…”