Skurray R A, Rouch D A, Lyon B R, Gillespie M T, Tennent J M, Byrne M E, Messerotti L J, May J W
Department of Microbiology, Monash University, Clayton, Victoria, Australia.
J Antimicrob Chemother. 1988 Apr;21 Suppl C:19-39. doi: 10.1093/jac/21.suppl_c.19.
Molecular and genetic analysis of multiresistant isolates of Staphylococcus aureus from widely separated hospitals in Australia has demonstrated that these are clearly related, and that the predominant strains possess up to three different plasmids, which fall into the following classes: (i) small 1.6 kb plasmids, such as pSK3, which are phenotypically cryptic, (ii) 4.5 kb chloramphenicol resistance plasmids, such as pSK2, and (iii) the pSK1 family of multiresistance plasmids, which range in size from 20 to 42 kb and variously encode resistance to antiseptics and disinfectants, trimethoprim (Tpr), penicillin (Pcr) and the aminoglycosides gentamicin, tobramycin and kanamycin (Gmr Tmr Kmr). Gmr Tmr Kmr is encoded on the pSK1 family plasmids by transposon Tn4001, which was also detected on the chromosomes of some clinical isolates. Tn4001 is composed of inverted repeats of the insertion sequence IS256; these repeats flank a Gmr Tmr Kmr sequence encoding for a 57,000 dalton bifunctional protein with aminoglycoside acetyltransferase [AAC(6')] and phosphotransferase [APH(2")] activities. A Tn4001-like structure, which is defective in transposition but encodes for a Gmr Tmr Kmr determinant homologous with that on Tn4001, occurs on conjugative plasmids from strains isolated in North America. Physical studies indicate that Pcr, via a beta-lactamase, and Tpr, via a trimethoprim-insensitive dihydrofolate reductase (DHFR), are also encoded on the pSK1 family by transposons; these transposons have been designated Tn4002 and Tn4003, respectively. Tn4003 is flanked by direct repeats of the insertion sequence IS257. The evolution of the pSK1 family of multiresistance plasmids is traced through the transposition and genetic rearrangement of resistance determinants. Transposition and genetic rearrangement have also contributed to the evolution of a multiresistant chromosome in Staph. aureus. In the majority of contemporary multiply resistant Staph. aureus strains the determinants for resistance to erythromycin (Emr), fusidic acid, methicillin (Mcr), minocycline, rifampicin, spectinomycin, streptomycin, sulphonamides, tetracycline (Tcr), cadmium (Cdr), and mercury (Hgr) are chromosomally encoded; these strains also possess chromosomally encoded Pcr, via a beta-lactamase. Evidence indicates that some of these determinants, Pcr, Cdr, Hgr, and Tcr, were plasmid encoded in isolates collected from Australian hospitals prior to 1970. Through transposition and site-specific integration, they have since been acquired by the chromosome in more recent Staph. aureus strains.(ABSTRACT TRUNCATED AT 400 WORDS)
对来自澳大利亚各地医院的耐多药金黄色葡萄球菌分离株进行的分子和基因分析表明，这些分离株明显相关，并且主要菌株拥有多达三种不同的质粒，可分为以下几类：(i) 小型1.6 kb质粒，如pSK3，其表型为隐蔽型；(ii) 4.5 kb氯霉素抗性质粒，如pSK2；(iii) pSK1多抗性质粒家族，大小从20到42 kb不等，不同程度地编码对抗菌剂和消毒剂、甲氧苄啶（Tpr）、青霉素（Pcr）以及氨基糖苷类庆大霉素、妥布霉素和卡那霉素（Gmr Tmr Kmr）的抗性。Gmr Tmr Kmr由转座子Tn4001编码在pSK1家族质粒上，在一些临床分离株的染色体上也检测到了Tn4001。Tn4001由插入序列IS256的反向重复序列组成；这些重复序列侧翼是一个Gmr Tmr Kmr序列，编码一种具有氨基糖苷乙酰转移酶[AAC(6')]和磷酸转移酶[APH(2")]活性的57,000道尔顿双功能蛋白。一种类似Tn4001的结构，其转座功能有缺陷，但编码与Tn4001上同源的Gmr Tmr Kmr决定簇，存在于从北美分离的菌株的接合质粒上。物理研究表明，Pcr通过一种β-内酰胺酶编码，Tpr通过一种对甲氧苄啶不敏感的二氢叶酸还原酶（DHFR）编码，它们也由转座子编码在pSK1家族上；这些转座子分别被命名为Tn4002和Tn4003。Tn4003侧翼是插入序列IS257的正向重复序列。通过抗性决定簇的转座和基因重排来追踪pSK1多抗性质粒家族的进化。转座和基因重排也促成了金黄色葡萄球菌中多抗性染色体的进化。在大多数当代多重耐药金黄色葡萄球菌菌株中，对红霉素（Emr）、夫西地酸、甲氧西林（Mcr）、米诺环素、利福平、壮观霉素、链霉素、磺胺类、四环素（Tcr）、镉（Cdr）和汞（Hgr）的抗性决定簇是染色体编码的；这些菌株还通过一种β-内酰胺酶拥有染色体编码的Pcr。有证据表明，在1970年之前从澳大利亚医院收集的分离株中，这些决定簇中的一些，如Pcr、Cdr、Hgr和Tcr，是质粒编码的。从那时起，通过转座和位点特异性整合，它们已被最近的金黄色葡萄球菌菌株的染色体获得。（摘要截短于400字）
