Asia-Pacific Centre for Animal Health, Melbourne Veterinary School, The University of Melbourne, Australia.
Metabolomics Australia, The Bio21 Institute of Molecular Science and Biotechnology, The University of Melbourne, Australia.
Vaccine. 2023 May 16;41(21):3358-3366. doi: 10.1016/j.vaccine.2023.04.045. Epub 2023 Apr 24.
The live attenuated temperature sensitive vaccine strain MS-H (Vaxsafe® MS, Bioproperties Pty. Ltd., Australia) is widely used to control disease associated with M. synoviae infection in commercial poultry. MS-H was derived from a field strain (86079/7NS) through N-methyl-N'-nitro-N-nitrosoguanidine (NTG)-induced mutagenesis. Whole genomic sequence analysis of the MS-H and comparison with that of the 86079/7NS have found that MS-H contains 32 single nucleotide polymorphisms (SNPs). Three of these SNPs, found in the obgE, oppF and gapdh genes, have been shown to be prone to reversion under field condition, albeit at a low frequency. Three MS-H reisolates containing the 86079/7NS genotype in obgE (AS2), obgE and oppF (AB1), and obgE, oppF and gapdh (TS4), appeared to be more immunogenic and transmissible compared to MS-H in chickens. To investigate the influence of these reversions in the in vitro fitness of M. synoviae, the growth kinetics and steady state metabolite profiles of the MS-H reisolates, AS2, AB1 and TS4, were compared to those of the vaccine strain. Steady state metabolite profiling of the reisolates showed that changes in ObgE did not significantly influence the metabolism, while changes in OppF was associated with significant alterations in uptake of peptides and/or amino acids into the M. synoviae cell. It was also found that GAPDH plays a role in metabolism of the glycerophospholipids as well as an arginine deiminase (ADI) pathway. This study underscores the role of ObgE, OppF and GAPDH in M. synoviae metabolism, and suggests that the impaired fitness arising from variations in ObgE, OppF and GAPDH contributes to attenuation of MS-H.
活疫苗减毒株 MS-H（Vaxsafe® MS，Bioproperties Pty. Ltd.，澳大利亚）广泛用于控制商业家禽中与滑液支原体感染相关的疾病。MS-H 是通过 N-甲基-N'-硝基-N-亚硝基胍（NTG）诱导诱变从田间分离株（86079/7NS）衍生而来。MS-H 的全基因组序列分析及其与 86079/7NS 的比较发现，MS-H 含有 32 个单核苷酸多态性（SNP）。在 obgE、oppF 和 gapdh 基因中发现的这 3 个 SNP 已被证明在田间条件下容易回复，但频率较低。在 obgE 中含有 86079/7NS 基因型的三个 MS-H 再分离株（AS2）、obgE 和 oppF（AB1）以及 obgE、oppF 和 gapdh（TS4）在鸡中似乎比 MS-H 更具免疫原性和传染性。为了研究这些回复在滑液支原体体外适应性中的影响，比较了 MS-H 再分离株 AS2、AB1 和 TS4 的生长动力学和稳态代谢物谱与疫苗株。再分离株的稳态代谢物谱分析表明，ObgE 的变化并未显著影响代谢，而 OppF 的变化与肽和/或氨基酸进入滑液支原体细胞的摄取显著改变有关。还发现 GAPDH 在甘油磷脂代谢以及精氨酸脱氨酶（ADI）途径中发挥作用。这项研究强调了 ObgE、OppF 和 GAPDH 在滑液支原体代谢中的作用，并表明 ObgE、OppF 和 GAPDH 变化引起的适应性降低导致 MS-H 的减毒。
