Whole Genome Analysis Reveals New Insights into Macrolide Resistance in Mycoplasma pneumoniae

Objective Mutations in 23 S rRNA gene are known to be associated with macrolide resistance in Mycoplasma pneumoniae（M. pneumoniae）. However, these mutations alone do not fully explain the high resistance rates in Asia. The aim of this study was to investigate other possible mutations involved in macrolide resistance in M. pneumoniae. Methods The whole genomes of 10 clinical isolates of M. pneumoniae with macrolide resistance were sequenced by Illumina Hi Seq2000 platform. The role of the macrolide-specific efflux transporter was assessed by efflux-pump inhibition assays with reserpine and carbonyl cyanide m-chlorophenyl-hydrazone（CCCP）. Results A total of 56 single nucleotide polymorphisms（SNPs） were identified in 10 clinical isolates in comparison to the reference strains M129 and FH. Strikingly, 4 of 30 SNPs causing non-synonymous mutations were clustered in macrolide-specific efflux system gene mac B encoding macrolide-specific efflux pump protein of the ATP-binding cassette transporter family. In assays of the minimal inhibitory concentrations（MIC） of macrolide antibiotics in the presence of the efflux pump inhibitors caused a significant decrease of MICs, even under detectable levels in some strains. Conclusion Our study suggests that macrolide efflux pump may contribute to macrolide resistance in M. pneumoniae in addition to the common point mutations in 23 S r RNA gene.

Ka-band ultra low voltage miniature sub-harmonic resistive mixer with a new broadside coupled Marchand balun in 0.18-μm CMOS technology

A Ka-band sub-harmonically pumped resistive mixer （SHPRM） was designed and fabricated using the standard 0.18-μm complementary metal-oxide-semiconductor （CMOS） technology. An area-effective asymmetric broadside coupled spiral Marchand balance-to-unbalance （balun） with magnitude and phase imbalance compensation is used in the mixer to transform local oscillation （LO） signal from single to differential mode. The results showed that the SHPRM achieves the conversion gain of -15- -12.5 dB at fixed fIF=0.5 GHz with 8 dBm LO input power for the radio frequency （RF） bandwidth of 28 35 GHz. The in-band LO-intermediate freqency （IF）, RF-IF, and LO-RF isolations are better than 31, 34, and 36 dB, respectively. Besides, the 2LO-IF and 2LO-RF isolations are better than 60 and 45 dB, respectively. The measured input referred PIdB and 3rd-order inter-modulation intercept point （IIP3） are 0.5 and 10.5 dBm, respectively. The measurement is performed under a gate bias voltage as low as 0.1 V and the whole chip only occupies an area of 0.33 mm^2 including pads.