Dolosigranulum pigrum cooperation and competition in human nasal microbiota

Abstract

25Background: Multiple epidemiological studies identify Dolosigranulum pigrum as a 26 candidate beneficial bacterium based on its positive association with health, including 27 negative associations with nasal/nasopharyngeal colonization by the pathogenic 28 species Staphylococcus aureus and Streptococcus pneumoniae. 29Results: Using a multipronged approach to gain new insights into D. pigrum function, 30 we observed phenotypic interactions and predictions of genomic capacity that support a 31 role for microbe-microbe interactions involving D. pigrum in shaping the composition of 32 human nasal microbiota. We identified in vivo community-level and in vitro phenotypic 33 cooperation by specific nasal Corynebacterium species. Also, D. pigrum inhibited S. 34 aureus growth in vitro. Whereas, robust inhibition of S. pneumoniae required both D. 35 pigrum and a nasal Corynebacterium together, and not either alone. D. pigrum L-lactic- 36 acid production was insufficient to account for these inhibitions. Genomic analysis of 11 37 strains revealed that D. pigrum has a small genome (average 1.86 Mb) and multiple 38 predicted auxotrophies consistent with D. pigrum relying on its human host and 39 cocolonizing bacteria for key nutrients. Further, the accessory genome of D. pigrum 40 3 encoded a diverse repertoire of biosynthetic gene clusters, some of which may have a 41 role in microbe-microbe interactions. 42 Conclusions: These new insights into D. pigrum's functions advance the field from 43 compositional analysis to genomic and phenotypic experimentation on a potentially 44 beneficial bacterial resident of the human upper respiratory tract and lay the foundation 45 for future animal and clinical experiments. 46 47 48 Streptococcus pneumoniae, microbe-microbe interactions, interspecies interactions, 50 upper respiratory tract, nasal, microbiota, comparative genomics 51 4 Background 52 Colonization of the human nasal passages by Staphylococcus aureus or Streptococcus 53pneumoniae is a major risk factor for infection by the colonizing bacterium at a distant 54 body site [1][2][3][4][5]. Interventions that reduce the prevalence of colonization also reduce the 55 risk of infection and transmission, e.g., as in [6, 7]. S. aureus and S. pneumoniae are 56 major human pathogens that cause significant morbidity and mortality worldwide [8][9][10][11]. 57 There are also concerns regarding rising rates of antimicrobial resistance [12] and the 58 potential for long-term effects of antibiotics early in life [13]. Thus, efforts have recently 59 focused on the identification of candidate bacteria that confer colonization resistance 60 against S. aureus [14-21] and S. pneumoniae [22-25], with particular urgency for S. 61 aureus in the absence of an effective vaccine. 62 Dolosigranulum pigrum has emerged in multiple studies of the human upper respiratory 63 tract microbiota, colonizing with or without Corynebacterium species, as potentially 64 beneficial and/or protective against colonization by S. aureus and ...

Intranasal Application of Lactococcus lactis W136 Is Safe in Chronic Rhinosinusitis Patients With Previous Sinus Surgery

“…Intriguingly, it may also have a role in regulation of other pathogens and is considered to play a key role in inflammatory disorders of the nose, nasopharynx, and paranasal sinuses (Brugger et al, 2016 ). Working alone, in vitro it is capable of inhibiting the growth of S. aureus , and, in combination with Corynebacterium pseudodipthericum , it is capable of inhibiting the growth of Streptococcus pneumoniae and Haemophilus influenzae (Brugger et al, 2020 ). D. pigrum has been suggested as a novel “probiotic” bacteria (Lappan and Peacock, 2019 ).…”

Quantifying variation in bacterial reproductive fitness with and without antimicrobial resistance: a high-throughput method

“…As at least in the early phase of growth, nutrient-competition effects seem to be minimal [12], the reason for this interaction could not yet be determined by baQFA. It could be hypothesised that with our baQFA method, bacterial interactions beyond competition for nutrients might be quantified, as they have been described similarly in vivo and in vitro [13,14]. Although we regard the results from our method adaptation work to only be of an exploratory nature, we could observe a substantially increased fitness in the methicillin resistant JE2 strain compared to the methicillin-susceptible Cowan strain, suggesting a different baseline-fitness of the underlying USA300 background in JE2 compared to Cowan, or the presence of compensatory mutations or other mechanisms of fitness gain.…”

Impact of Temporal pH Fluctuations on the Coexistence of Nasal Bacteria in an in silico Community

“…Six strains used in this study were isolated from two healthy individuals and kindly shared with us by Dr. Katherine Lemon ( Table 1 ). Interactions between some of these strains and other nasal bacteria has been studied recently ( Brugger et al, 2020 ).…”

“…Many factors, including interspecies interactions ( Bomar et al, 2016 ; Brugger et al, 2016 , 2020 ), the host immune system ( Johannessen et al, 2012 ), and resource availability and access ( Relman, 2012 ) can impact the nasal microbiota. However, all these factors take place in an environment that may fluctuate over time and vary in space.…”

“…To answer the above question, we first characterize six nasal bacterial isolates as representative of members present in the nasal community. The rationale behind choosing these nasal bacteria was that (1) we can culture these strains reliably in the same cultivation medium and conditions in the lab; (2) covering different Corynebacterium and Staphylococcus species, these strains capture some of the natural diversity of microbiota ( Escapa et al, 2018 ); and (3) Some interactions among these strains has already been identified ( Brugger et al, 2020 ). For instance, Corynebacterium have been used to inhibit S. aureus colonization ( Uehara et al, 2000 ; Kiryukhina et al, 2013 ) and S. aureus promotes the growth of C. accolens and gets inhibited by C. pseudodiphtheriticum ( Yan et al, 2013 ).…”