Staph Aureus Sepsis Model

In the BALB/c mouse sepsis model, animals are challenged with an intraperitoneal (IP) injection of S. aureus strain with or without 3% mucin. In the mucin model, mice are challenged via injection with the study specific strain in 3% mucin as previously described (Adhikari, et al, 2012; Fattom, et al, 1996) and even low challenge dose (104-5 CFU/ mouse) lead to death. In the non-mucin model, animals receive challenge inoculum without mucin and a higher challenge dose (107-9 CFU/ mouse) is required to achieve LD90.

In both models the animals are monitored for morbidity and mortality twice a day for 14 days post challenge. The mucin model allows for incremental increases in the challenge dose to differentiate dose response at broader ther- apeutic ranges. We have established LD50 values for various strain using this model; typically, lethality occurs within 24-48 hours post infection.

Staph Sepsis

Fig. 1 Survival after challenge with INFV H1N1 A/Pert/261/2009 (Tamiflu-resistant strain). Inoculum 1xLD90=1.0E+05 PFU/mouse
Survival after challenge with INFV H1N1 A/Pert/261/2009 (Tamiflu-resistant strain) 1.0E+05 PFU/mouse
Survival and weight change in BALB/c mice challenged with INFV A/ Texas/36/91 (H1N1) and treated with antiviral Osletamivir Phosphate (Tamiflu)
Lung viral load and Survival (30 % weight loss cut-off) in BALB/c mice challenged with INFV H3N2 A/HK/1/68.

Alpha (UK) – B. 1.1.7 / 501Y.V1

amino acid mutations: del69–70 HV, del144 Y, N501Y, A570D, D614G, P681H, T761I, S982A, D1118H

Beta (South Africa) – B.1.351

amino acid mutations: K417N, E484K, N501Y, D614G, A701V

Gamma (Brazil) – P.1

amino acid mutations: L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I

Epsilon (Ca, USA) B.1.427

amino acid mutations: L452R, D614G

SARS-CoV-2 Parental Strain Wild Type (Wuhan)
SARS-CoV-2 D614G Variant

amino acid mutations: D614G

Epsilon (Ca, USA) B.1.429

amino acid mutations: S13I, W152C, L452R, D614G

SARS-CoV-2 Delta Variant

amino acid mutations: L452R, E484Q