nasopharyngeal colonization
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Author(s):  
Laura Willen ◽  
Esra Ekinci ◽  
Lize Cuypers ◽  
Heidi Theeten ◽  
Stefanie Desmet

Streptococcus pneumoniae is an important and frequently carried respiratory pathogen that has the potential to cause serious invasive diseases, such as pneumonia, meningitis, and sepsis. Young children and older adults are among the most vulnerable to developing serious disease. With the arrival of the COVID-19 pandemic and the concomitant restrictive measures, invasive disease cases caused by respiratory bacterial species, including pneumococci, decreased substantially. Notably, the stringency of the containment measures as well as the visible reduction in the movement of people appeared to coincide with the drop in invasive disease cases. One could argue that wearing protective masks and adhering to social distancing guidelines to halt the spread of the SARS-CoV-2 virus, also led to a reduction in the person-to-person transmission of respiratory bacterial species. Although plausible, this conjecture is challenged by novel data obtained from our nasopharyngeal carriage study which is performed yearly in healthy daycare center attending children. A sustained and high pneumococcal carriage rate was observed amid periods of stringent restrictive measures. This finding prompts us to revisit the connection between nasopharyngeal colonization and invasion and invites us to look closer at the nasopharyngeal microbiome as a whole.


Author(s):  
Carina Valente ◽  
Ana R. Cruz ◽  
Adriano O. Henriques ◽  
Raquel Sá-Leão

Streptococcus pneumoniae is a human pathogen responsible for high morbidity and mortality worldwide. Disease is incidental and is preceded by asymptomatic nasopharyngeal colonization in the form of biofilms. Simultaneous colonization by multiple pneumococcal strains is frequent but remains poorly characterized. Previous studies, using mostly laboratory strains, showed that pneumococcal strains can reciprocally affect each other’s colonization ability. Here, we aimed at developing a strategy to investigate pneumococcal intra-species interactions occurring in biofilms. A 72h abiotic biofilm model mimicking long-term colonization was applied to study eight pneumococcal strains encompassing 6 capsular types and 7 multilocus sequence types. Strains were labeled with GFP or RFP, generating two fluorescent variants for each. Intra-species interactions were evaluated in dual-strain biofilms (1:1 ratio) using flow cytometry. Confocal microscopy was used to image representative biofilms. Twenty-eight dual-strain combinations were tested. Interactions of commensalism, competition, amensalism and neutralism were identified. The outcome of an interaction was independent of the capsular and sequence type of the strains involved. Confocal imaging of biofilms confirmed the positive, negative and neutral effects that pneumococci can exert on each other. In conclusion, we developed an experimental approach that successfully discriminates pneumococcal strains growing in mixed biofilms, which enables the identification of intra-species interactions. Several types of interactions occur among pneumococci. These observations are a starting point to study the mechanisms underlying those interactions.


2021 ◽  
Author(s):  
Jorge E. Vidal ◽  
Meagan N. Wier ◽  
Uriel Angulo-Zamudio ◽  
Erin McDevitt ◽  
Ana G. Jop Vidal ◽  
...  

Streptococcus pneumoniae (Spn) colonizes the nasopharynx of children and the elderly but also kills millions worldwide yearly. The secondary bile acid metabolite, deoxycholic acid (DoC), affects the viability of human pathogens but also plays multiple roles in host physiology. We assessed in vitro the antimicrobial activity of DoC and investigated its potential to eradicate Spn colonization using a model of human nasopharyngeal colonization and an in vivo mouse model of colonization. At a physiological concentration DoC (0.5 mg/ml; 1.27 mM) killed all tested Spn strains (N=48) two hours post-inoculation. The model of nasopharyngeal colonization showed that DoC eradicated colonization by Spn strains as soon as 10 min post-exposure. The mechanism of action did not involve activation of autolysis since the autolysis-defective double mutants Δ lytA Δ lytC and ΔspxBΔlctO were as susceptible to DoC as was the wild-type (WT). Oral streptococcal species (N=20), however, were not susceptible to DoC (0.5 mg/ml). Unlike trimethoprim, whose spontaneous resistance frequency (srF) for TIGR4 or EF3030 was ≥1x10 −9 , no spontaneous resistance was observed with DoC (srF≥1x10- 12 ). Finally, the efficacy of DoC to eradicate Spn colonization was assessed in vivo using a topical route via intranasal (i.n.) administration and as a prophylactic treatment. Mice challenged with Spn EF3030 carried a median of 4.05x10 5 cfu/ml four days post-inoculation compared to 6.67x10 4 cfu/ml for mice treated with DoC. Mice in the prophylactic group had a ∼99% reduction of the pneumococcal density (median, 2.61 x10 3 cfu/ml). Thus, DoC, an endogenous human bile salt, has therapeutic potential against Spn.


2021 ◽  
Author(s):  
Breno A B Salgado ◽  
Elaine Waters ◽  
Josephine Chantale Moran ◽  
Aras Kadioglu ◽  
Malcolm James Horsburgh

Staphylococcus aureus nasal colonization is a risk factor for infection. A large proportion of the population are identified as potential S. aureus carriers yet we only partially understand the repertoire of genetic factors that promote long-term nasal colonization. Here we present a novel murine model of nasopharyngeal colonization that requires a low S. aureus inoculum and is amenable to experimental evolution approaches. We used this model to experimentally evolve S. aureus using successive passages in the nasopharynx to identify those genetic loci under selection. After 3 cycles of colonization, mutations were identified in mannitol, sorbitol, arginine, nitrite and lactate metabolism genes promoting key pathways in nasal colonization. Stress responses were identified as being under selective pressure, with mutations in DNA repair genes including dnaJ and recF and key stress response genes clpL, rpoB and ahpF . Peptidoglycan synthesis pathway genes also revealed mutations indicating potential selection for alteration of the cell surface. The infection model used here is versatile to assist decolonization and persistence studies.


2021 ◽  
Vol 9 ◽  
Author(s):  
Ravinder Kaur ◽  
Steven Schulz ◽  
Naoko Fuji ◽  
Michael Pichichero

Background: The coronavirus disease 2019 (COVID-19) pandemic led to day care and school closures and children staying home for several months. When they gradually returned, aggressive regulations were implemented in New York State to reduce viral transmission.Method: An ongoing prospective study occurring in the Rochester, NY region, focused on early childhood respiratory infectious diseases, afforded an opportunity to assess the impact of the pandemic on the incidence of these illnesses in a primary care outpatient setting. Physician-diagnosed, medically attended infection visits were assessed in two child cohorts, age 6–36 months old: from March 15 to December 31, 2020 (the pandemic period) compared to the same months in 2019 (prepandemic). Nasopharyngeal colonization by potential otopathogens during healthy/well-child and acute otitis media (AOM) visits was evaluated.Results: One hundred and forty-four children were included in the pandemic cohort and 215 in the prepandemic cohort. The pandemic cohort of children experienced 1.8-fold less frequent infectious disease visits during the pandemic (p < 0.0001). Specifically, visits for AOM were 3.7-fold lower (p < 0.0001), viral upper respiratory infections (URI) 3.8-fold lower (p < 0.0001), croup 27.5-fold lower (p < 0.0001), and bronchiolitis 7.4-fold lower (p = 0.04) than the prepandemic cohort. Streptococcus pneumoniae (p = 0.03), Haemophilus influenzae (p < 0.0001), and Moraxella catarrhalis (p < 0.0001) nasopharyngeal colonization occurred less frequently among children during the pandemic.Conclusion: In primary care pediatric practice, during the first 9 months of the COVID-19 pandemic, significant decreases in the frequency of multiple respiratory infections and nasopharyngeal colonization by potential bacterial respiratory pathogens occurred in children age 6–36 months old.


2021 ◽  
Vol 118 (32) ◽  
pp. e2019923118
Author(s):  
Nadia A. Kadry ◽  
Eric A. Porsch ◽  
Hao Shen ◽  
Joseph W. St. Geme

Nontypeable Haemophilus influenzae (NTHi) is a common cause of localized respiratory tract disease and results in significant morbidity. The pathogenesis of NTHi disease begins with nasopharyngeal colonization, and therefore, the prevention of colonization represents a strategy to prevent disease. The NTHi HMW1 and HMW2 proteins are a family of conserved adhesins that are present in 75 to 80% of strains and have been demonstrated to play a critical role in colonization of the upper respiratory tract in rhesus macaques. In this study, we examined the vaccine potential of HMW1 and HMW2 using a mouse model of nasopharyngeal colonization. Immunization with HMW1 and HMW2 by either the subcutaneous or the intranasal route resulted in a strain-specific antibody response associated with agglutination of bacteria and restriction of bacterial adherence. Despite the specificity of the antibody response, immunization resulted in protection against colonization by both the parent NTHi strain and heterologous strains expressing distinct HMW1 and HMW2 proteins. Pretreatment with antibody against IL-17A eliminated protection against heterologous strains, indicating that heterologous protection is IL-17A dependent. This work demonstrates the vaccine potential of the HMW1 and HMW2 proteins and highlights the importance of IL-17A in protection against diverse NTHi strains.


2021 ◽  
Author(s):  
Jorge E. Vidal ◽  
Meagan N. Wier ◽  
Uriel Angulo-Zamudio ◽  
Erin McDevitt ◽  
Ana G Vidal ◽  
...  

Streptococcus pneumoniae (Spn) colonizes the nasopharynx of children and the elderly but also kills millions worldwide yearly. The secondary bile acid metabolite, deoxycholic acid (DoC), affects the viability of human pathogens but also plays multiple roles in host physiology. We assessed in vitro the antimicrobial activity of DoC and investigated its potential to eradicate Spn colonization using an ex vivo model of human nasopharyngeal colonization and an in vivo mouse model of colonization. At a physiological concentration DoC (0.5 mg/ml; 1.27 mM) killed all tested Spn strains (N=48) two h post-inoculation. The ex-vivo model of nasopharyngeal colonization showed that DoC eradicated colonization by Spn strains as soon as 10 min post-exposure. The mechanism of action did not involve activation of autolysis since the autolysis-defective double mutants ΔlytAΔlytC and ΔspxBΔlctO were as susceptible to DoC as was the wild-type (WT). Oral streptococcal species (N=20), however, were not susceptible to DoC (0.5 mg/ml). Unlike trimethoprim, whose spontaneous resistance frequency (srF) for TIGR4 or EF3030 was ≥1x10-9, no spontaneous resistance was observed with DoC (srF≥1x10-12). Finally, the efficacy of DoC to eradicate Spn colonization was assessed in vivo using a topical route via intranasal (i.n.) administration and as a prophylactic treatment. Mice challenged with Spn EF3030 carried a median of 4.05x105 cfu/ml four days post-inoculation compared to 6.67x104 cfu/ml for mice treated with DoC. Mice in the prophylactic group had a ~99% reduction of the pneumococcal density (median, 2.61 x103 cfu/ml). Thus, DoC, an endogenous human bile salt, has therapeutic potential against Spn.


Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 187
Author(s):  
Antonio J. Martín-Galiano ◽  
María S. Escolano-Martínez ◽  
Bruno Corsini ◽  
Adela G. de la Campa ◽  
José Yuste

Knowledge-based vaccinology can reveal uncharacterized antigen candidates for a new generation of protein-based anti-pneumococcal vaccines. DiiA, encoded by the sp_1992 locus, is a surface protein containing either one or two repeats of a 37mer N-terminal motif that exhibits low interstrain variability. DiiA belongs to the core proteome, contains several conserved B-cell epitopes, and is associated with colonization and pathogenesis. Immunization with DiiA protein via the intraperitoneal route induced a strong IgG response, including different IgG subtypes. Vaccination with DiiA increased bacterial clearance and induced protection against sepsis, conferring 70% increased survival at 48 h post-infection when compared to the adjuvant control. The immunogenic response and survival rates in mice immunized with a truncated DiiA version lacking 119 N-terminal residues were remarkably lower, confirming the relevance of the repeat zone in the immunoprotection by DiiA. Intranasal immunization of mice with the entire recombinant protein elicited mucosal IgG and IgA responses that reduced bacterial colonization of the nasopharynx, confirming that this protein might be a vaccine candidate for reducing the carrier rate. DiiA constitutes an example of how functionally unannotated proteins may still represent promising candidates that can be used in prophylactic strategies against the pneumococcal carrier state and invasive disease.


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