Steroidal alkaloids and conessine from the medicinal plant Holarrhena antidysenterica restore antibiotic efficacy in a Galleria mellonella model of multidrug-resistant Pseudomonas aeruginosa infection

Table 2 Effect of conessine and steroidal alkaloids in combination with levofloxacin on the viability of P. aeruginosa PAM1020, PAM1032 and PAM1034

	Strain	Agent (s)	Concentration (mg/L)	Log CFU/ml
	Strain	Agent (s)	Concentration (mg/L)	Inoculum	Untreated control	Treatment (±SD)	Log reduction
Single treatment at MIC_0.5^a	PAM1020	Conessine	32			9.47 ± 0.03	0.27
		Alkaloids	1024	5.16 ± 0.06	9.74 ± 0.06	8.76 ± 0.01	0.98
		LVX	0.125			8.91 ± 0.02	0.83
	PAM1032	Conessine	32			9.42 ± 0.01	0.45
		Alkaloids	1024	5.44 ± 0.08	9.87 ± 0.14	8.82 ± 0.06	1.05
		LVX	1			8.19 ± 0.68	1.68
	PAM1034	Conessine	32			9.54 ± 0.09	0.13
		Alkaloids	1024	5.64 ± 0.21	9.67 ± 0.02	8.88 ± 0.23	0.79
		LVX	2			8.18 ± 0.10	1.49
Combinations at MIC_0.5	PAM1020	Conessine + LVX	32 + 0.125	5.16 ± 0.06	9.74 ± 0.06	9.25 ± 0.03	0.49
		Alkaloids + LVX	1024 + 0.125			8.12 ± 0.16	1.62
	PAM1032	Conessine + LVX	32 + 1	5.44 ± 0.08	9.87 ± 0.14	5.35 ± 0.43	4.52
		Alkaloids + LVX	1024 + 1			7.70 ± 0.13	2.17
	PAM1034	Conessine + LVX	32 + 2	5.64 ± 0.21	9.67 ± 0.02	5.54 ± 0.09	4.13
		Alkaloids + LVX	1024 + 2			6.85 ± 0.67	2.82

^aA MIC was not detectable for the steroidal alkaloids so the highest concentration tested was used in this assay
Viability was determined in 96-well microplates after 24 h exposure to the antibiotics in MHB at 37 °C. Data shown is the mean and standard deviation from quadruple experiments. Highlighted treatments are those that resulted in ≥2 log₁₀ reduction compared to untreated controls

ISSN: 2662-7671