Capture and visualization of live Mycobacterium tuberculosis bacilli from tuberculosis patient bioaerosols

Dinkele, Ryan; Gessner, Sophia; McKerry, Andrea; Leonard, Bryan; Seldon, Ronnett; Koch, Anastasia; Morrow, Carl; Gqada, Melitta; Kamariza, Mireille; Bertozzi, Carolyn R.; Smith, Brian R.; McLoud, Courtney; Kamholz, Andrew Evan; Bryden, Wayne A.; Call, Charles J.; Kaplan, Gilla; Mizrahi, Valerie; Wood, Robin; Warner, Digby F.

doi:10.1371/journal.ppat.1009262

Cited by 41 publications

(54 citation statements)

References 39 publications

(48 reference statements)

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“…During the middle five manoeuvres, 100 L/minute of exhaled air was diverted via the APS. New cyclone collectors were attached after each sample allowing for the independent enumeration of Mtb utilising our previously described concentration and visualisation pipeline (8).…”

Section: Sample Collectionmentioning

confidence: 99%

“…Bioaerosols were stained with DMN-trehalose (DMN-tre) (Olilux Biosciences Inc.) and visualised as previously outlined (8). Briefly, liquid-captured bioaerosols (5 -10 mL) were centrifuged for 10 minutes at 3000 x g (Allegra X-15R, Beckman Coulter) and resuspended in 200 µL of Middlebrook 7H9 medium supplemented with 100 µM DMN-tre.…”

Section: Staining and Visualisation Of Bioaerosol Samplesmentioning

confidence: 99%

“…We have developed a platform combining non-invasive bioaerosol capture technology and fluorescence microscopy to enumerate viable Mtb released by confirmed TB patients (7)(8)(9). Using this platform, we detected Mtb bacilli in the absence of (induced) Cough.…”

Section: Introductionmentioning

confidence: 99%

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Aerosolization of Mycobacterium tuberculosis by tidal breathing

Dinkele

Gessner

McKerry

et al. 2021

Preprint

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Rationale: Interrupting tuberculosis (TB) transmission requires an improved understanding of how - and when - the causative organism, Mycobacterium tuberculosis (Mtb), is aerosolized. Although Cough is commonly assumed to be the dominant source of Mtb aerosols, recent evidence of Cough-independent Mtb release implies the contribution of alternative mechanisms. Objective: To compare the aerosolization of Mtb and particulate matter from GeneXpert-positive patients during three separate respiratory manoeuvres: Tidal Breathing (TiBr), Forced Vital Capacity (FVC), and Cough. Methodology: Bioaerosol sampling and Mtb detection were combined with real-time assessments of CO2 production and particle counts from 39 confirmed TB patients. Measurements and Main Results: TiBr and FVC produced comparable numbers of particles, with Cough producing >4-fold more. For all manoeuvres, the proportions of particles detected across size categories from 0.5 - 5 µm were similar, with minor differences observed only in particles between 1.5 - 2 µm (p = 0.014) and >5 µm (p = 0.020). Viable Mtb bacilli were detected in 66%, 70%, and 65% of TiBr, FVC, and Cough samples, respectively. Notably, while Cough produced 3-fold more Mtb than TiBr, the relative infrequency of coughing compared to breathing implies that TiBr likely contributes >90% of the daily aerosolised Mtb across a range of Cough frequencies. Conclusions: Our results suggest that, while Cough increases particle aerosolization compared to TiBr, this is not associated with increased Mtb aerosolization. Instead, TiBr produces more Mtb per particle than Cough. Assuming the number of viable Mtb organisms detected provides a proxy measure of patient infectiousness, these observations imply a significant contribution of TiBr to TB transmission.

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Section: Sample Collectionmentioning

confidence: 99%

Section: Staining and Visualisation Of Bioaerosol Samplesmentioning

confidence: 99%

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Aerosolization of Mycobacterium tuberculosis by tidal breathing

Dinkele

Gessner

McKerry

et al. 2021

Preprint

Self Cite

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“…The copyright holder for this preprint (which this version posted May 19, 2021. ; https://doi.org/10.1101/2021.05. 19.444830 doi: bioRxiv preprint bioaerosols exhaled by patients with active pulmonary TB (9,11,12). Based on these observations, we hypothesize that host exposure to Mtb-AG, as opposed to single bacilli (Mtb-SC), may be an effective bacterial strategy for establishing an infection that is more likely to progress to active disease.…”

Section: Introductionmentioning

confidence: 99%

Aggregation state of Mycobacterium tuberculosis impacts host immunity and augments pulmonary disease pathology

Kolloli

Kumar

Singh

et al. 2021

Preprint

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Phagocytosis of Mycobacterium tuberculosis (Mtb) aggregates, rather than similar numbers of single bacilli, induces host macrophage death and favors bacterial growth. Here, we examined whether aggregation contributes to enhanced Mtb pathogenicity in vivo in rabbit lungs. Rabbits were exposed to infectious aerosols containing mainly Mtb-aggregates (Mtb-AG) or Mtb-single cells (Mtb-SC). The lung bacterial load, histology, and immune cell composition were investigated over time. Genome-wide transcriptome analysis, cellular and tissue-level assays, and immunofluorescent imaging were performed on lung tissue to define and compare differential immune activation and pathogenesis between Mtb-AG and Mtb-SC infection. Lung bacillary loads, disease scores, lesion size, and structure were significantly higher in Mtb-AG than in Mtb-SC infected animals. A differential immune cell distribution and activation were noted in the lungs and spleen of the two groups of infected animals. Mtb-AG infected animals also showed early induction of inflammatory network genes associated with necrosis and reduced host cell viability. Consistently, larger lung granulomas with clumped Mtb, extensive necrotic foci, and elevated matrix metalloproteases expression were observed in Mtb-AG infected rabbits. Our findings suggest that bacillary aggregation increases Mtb fitness for improved growth and accelerated lung inflammation and cell death, thereby exacerbating disease pathology in the lungs.

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“…Live bacilli from smear positive case can cause pulmonary tuberculosis after inhalation [28]. Untreated patient with positive smear can spread the infection to nearly 10 persons within a year [29,30]. The infection of susceptible person depend on the concentration of the aerosol in the air [28].…”

Section: Smear Positive Pulmonary Tuberculosis (Ptb)mentioning

confidence: 99%

Mycobacterium Tuberculosis Control: An Overview

Okiki

Daramola

et al. 2021

JAMB

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Tuberculosis is an age-long disease that has proved challenging to eradicate. In 2019 about 10 million people fell ill of TB and it has caused 1.2 million deaths among HIV negative people and 208,000 deaths among HIV positive individuals [1]. The reduction in incidence rate between 2015 and 2019 was 9% and global target for 2030 is 80% [1]. For the achievement of the Sustainable Development Goals (SDGs) and WHO’s End TB Strategy the following should be considered; (1) breaking the transmission cascade of tuberculosis infection (2) effective management of the risk factors of spreading TB infection (3) administering workable preventive policy for individual health sector, and (4) prompt and effective standard control method. Tuberculosis infection is a must to eradicate, hence all stakeholders should come together for the patients, health care workers and policy makers to achieve End TB by 2035.

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Capture and visualization of live Mycobacterium tuberculosis bacilli from tuberculosis patient bioaerosols

Cited by 41 publications

References 39 publications

Aerosolization of Mycobacterium tuberculosis by tidal breathing

Aerosolization of Mycobacterium tuberculosis by tidal breathing

Aggregation state of Mycobacterium tuberculosis impacts host immunity and augments pulmonary disease pathology

Mycobacterium Tuberculosis Control: An Overview

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