Figure 4.

Netilmicin sulfate alone and in combination exerted protective effects on an infected C. elegans model

(A) Drug toxicity of NETS, CAZ, and NETS+CAZ to C. elegans. The abscissa represents the duration of continuous incubation with the drug C. elegans, and the survival rate was observed every 8 h. The ordinate is the survival rate of C. elegans. C. elegans: blank negative control group without drug incubation; the others are the drug groups. 30 μM NETS: C. elegans treated with 30 μM NETS. 3.75 μM CAZ: C. elegans treated with 3.75 μM CAZ. 30 μM NETS+1.88 μM CAZ: C. elegans treated with 30 μM NETS and 1.88 μM CAZ. The other groups are labeled in the same way.

(B and C) Protection efficacy of the drug on C. elegans (B: Early intervention; that is, C. elegans was infected with the bacteria after 2 h of incubation with the inhibitor. C: Late intervention, namely, introduction of the inhibitor 2 h after the infection of C. elegans.) The abscissa shows the duration of continuous incubation with the drug C. elegans, and the survival rate was observed every 8 h. The ordinate is the survival rate of C. elegans. C. elegans: blank negative control group. Bp: the infected C. elegans group. The other groups were infected C. elegans treated with drugs. Bp+60 μM NETS: infected C. elegans were treated with 60 μM NETS. Bp+30 μM NETS+1.88 μM CAZ: C. elegans were treated with 30 μM NETS and 1.88 μM CAZ. The other groups are labeled in the same way. (∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001. Data are represented as mean ± SEM.).

(D) Fluorescence Microscopy: The distribution and burden of DilC18-labeled Burkholderia pseudomallei within nematodes following early and late interventions with different antibiotics were investigated. NETS Group: infected C. elegans treated with BP + NETS. NETS + CAZ Group: C. elegans treated with BP + NETS + CAZ. CAZ Group: infected C. elegans treated with BP + CAZ. Untreated control group: infected C. elegans treated with BP only.