Property of Presenter. Not for Reproduction. Environmental Sources of NTM. Joseph O. Falkinham, III

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1 Environmental Sources of NTM Joseph O. Falkinham, III

2 Nontuberculous Mycobacteria Environmental Opportunistic Pathogens Almost 200 Mycobacterium species Community-Acquired Cervical Lymphadenitis Pulmonary Disease Skin Infections Hospital-Acquired Bacteremia Surgical Wound Infections 2

3 3 Major NTM Species Mycobacterium avium complex (MAC) M. avium (4 subspecies) Currently 8 other MAC species M. intracellulare versus M. chimaera M abscessus complex M. kansasii M. marinum M. fortuitum

4 Innate NTM Risk Factors Cervical Lymphadenitis Children, erupting teeth Pulmonary Disease Lung Damage (Smoking, COPD, Dust) Cystic Fibrosis GERD Taller, Slender, Older Women Bacteremia: Immunodeficiency 4

5 5 Behavioral NTM Risk Factors Shower aerosols Gardening dusts Exposure to humidifier aerosols Second homes with higher water-age Unoccupied wings of homes Water and ice from refrigerators Hot tub and spa aerosols Aquaria exposure (M. marinum)

6 F S F S C H C/H / S/F Patient/Control C P

7 Temperature Temp C 20 Flushed Stagnant Flushed Stagnant Flushed Stagnant Flushed Stagnant Cold Hot Cold Hot Least Used Most Used M/L / C/H / Stag/Flush

8 R²: Total NTM 4.0 C R²: P log Mspp (gc/ml) M. avium C P log Ma (gc/ml) Temperature C Temperature C

9 9 Natural Soils Sources of NTM Purchased Peat-rich Soils Natural Waters Piped Water and Premise Plumbing Water and Ice from Refrigerators Aerosols from Showers, Humidifiers, Spas Moldy Building Materials Medical Equipment (Heater-Coolers)

10 10 NTM in Premise Plumbing Entry via water distribution system Survive residual disinfectant (resistant) Growth in water-heater (heat-resistant) Circulation throughout house Biofilm-formation (adhere, grow, and persist) Stagnation (grow at low oxygen levels) Aerosolization from showers and taps Aerosolization via humidification

11 Total Chlorine Total Cl2 0.0 Flushed Stagnant Flushed Stagnant Flushed Stagnant Flushed Stagnant Cold Hot Cold Hot Least Used Most Used M/L / C/H / Stag/Flush

12 R²: Total NTM R²: C P log Mspp (gc/ml) M. avium C P log Ma (gc/ml) Total Cl Total Cl2

13 Pink-Slime in Showers Pink slime due to Methylobacterium NTM absent if Methylobacteria present Methylobacteria absent if NTM present Both readily form biofilms Methylobacterium biofilm prevents adherence of NTM 13

14 14 NTM Outer Membrane NTM have a true outer membrane C 60 -C 80 lipids 30 % of cell weight Cells are hydrophobic and impermeable Slow growth: due to diversion of resources reduced uptake of nutrients Benefits: resistant to antimicrobial agents hydrophobic cells aerosolized

15 Adapted to Built Environment Disinfectant-resistance Prefer adherence and biofilm formation Oligotrophic: grow on available carbon Growth from C Grow in water heaters Microaerobic - grow at 6 and 12 % O 2 Grow in amoebae 15

16 Zn Zinc F S F S F S F S C H C H L M Most/Least / C/H / S/F Zn

17 Total NTM R²: M. avium C P log Ma (gc/ml) log (Zn)

18 Adaptation Novel phenotype not due to mutation Phenotypic expression dependent upon continued exposure to selection Growth under non-selective conditions results in loss of novel phenotype NTM adaptation favored by: High Metabolism with Slow Growth 18

19 NTM Adaptation Adaptive biofilm antimicrobial resistance: Suspend biofilm-grown M. avium Suspended cells = antibiotic-resistant Adaptive thermal resistance: Grow M. avium at 42 C = Survive 60 C Grow M. avium at 25 C = Killed at 60 C 19