Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection

Whole-genome analyses reveal gene content differences between nontypeable Haemophilus influenzae isolates from chronic obstructive pulmonary disease compared to other clinical phenotypes

“…NTHi has developed mechanisms to thrive in the hostile environment of different anatomical regions, such as the middle ear, upper and lower respiratory tracts, blood and the meninges [5]. Evolutionary and ecological forces drive bacteria to adapt and grow in different niches [6][7][8][9] by utilizing the basic nutrients available and resisting toxic products present in its environment [10]. This evolutionary adaptation typically involves two fundamental processes.…”

“…During homologous recombination, a chromosomal fragment of a genome is replaced with a homologous sequence from another genome, whereas non-homologous recombination results in gain and loss of genetic material [14]. These processes can contribute to phenotypic changes including increased virulence and antibiotic resistance, and adaptations to the host microenvironments such as immune evasion and greater metabolic capacity [7,8,[15][16][17][18][19].…”

Learning from –omics strategies applied to uncover Haemophilus influenzae host-pathogen interactions: Current status and perspectives

“…This is the case of the mutation of the icc gene, encoding a 3́,5́-cyclic adenosine monophosphate phosphodiesterase, identified as a H. influenzae microevolution trait in response to transient nutrient limitation, which associates with increased development of intracellular bacterial communities (IBC) [60] . Likewise, when using a pre-clinical model of OM to assess NTHi pathoadaptation during sequential episodes of disease, microevolution of haemoglobin binding and LOS biosynthesis genes was observed in such OM-adapted strains, which in turn promoted increased biofilm formation, inflammation, stromal fibrosis, and an increased propensity to form IBCs [61] .…”

“…Methylome profiling [35] , [52] A5. Microevolution in experimental settings [60] , [61] B. Genome-wide genetic screening B1. HITS* based in vivo genetic screenings [12] , [67] , [68] B2.…”

Editorial: Otitis Media Genomics and the Middle Ear Microbiome

“…Overall, the findings in the articles included in this topic suggest that: (A) dysbiosis in the ME and NP microbiotas according to age, temporality with OM onset, and occurrence of LRT disease contribute to OM susceptibility; (B) although transcriptome studies identified novel genes and pathways that are involved in OM susceptibility, many more genes and pathways that are potential targets for novel therapies need to be validated or identified; and (C) animal models remain useful in elucidating mechanisms for OM susceptibility. Future meta -omic analyses will help in further understanding the metabolic functions and strain heterogeneity of bacteria in the ME and NP, and will enable detection of microbial factors (e.g., microbial genetic variants, serotypes) that favor resistance to antibiotics or antivirals, biofilm formation, immune evasion, metabolic efficiency, and virulence ( Pettigrew et al, 2002 ; Ecevit et al, 2004 ; Ehrlich et al, 2005 ; Shen et al, 2005 ; Pettigrew et al, 2006 ; Buchinsky et al, 2007 ; Hiller et al, 2011 ; Pettigrew et al, 2011 ; Thomas et al, 2011 ; Pettigrew et al, 2012 ; Lewnard et al, 2016 ; Hu et al, 2019 ; Hammond et al, 2020 ; Harrison et al, 2020 ). Virulence factors of otopathogens may also identify candidate antigens for novel vaccines ( Mottram et al, 2019 ).…”